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Journal of Investigative Dermatology
Journal Prestige (SJR): 2.282
Citation Impact (citeScore): 4
Number of Followers: 28  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0022-202X - ISSN (Online) 1523-1747
Published by Elsevier Homepage  [3281 journals]
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      Citation: Journal of Investigative Dermatology 141, 11 (2021)
      PubDate: 2021-11
      DOI: 10.1016/S0022-202X(21)02231-4
      Issue No: Vol. 141, No. 11 (2021)
       
  • SnapshotDx Quiz: November 2021

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      Authors: Meiqi Luo; Emily Y. Chu
      Abstract: Editorial note: Welcome to the Journal of Investigative Dermatology (JID) SnapshotDx Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis'”) relates to the clinical image shown, while additional questions concern the findings reported in a JID article by Guhan et al. (2021) (https://doi.org/10.1016/j.jid.2020.12.035).
      Citation: Journal of Investigative Dermatology 141, 11 (2021)
      PubDate: 2021-11
      DOI: 10.1016/j.jid.2021.08.398
      Issue No: Vol. 141, No. 11 (2021)
       
  • Cells to Surgery Quiz: November 2021

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      Authors: Brian Cheng; Surya Veerabagu, H. William Higgins
      Abstract: Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis'”) relates to the clinical image shown, while additional questions concern the findings reported in a JID article by Zhai et al. (2021) (https://doi.org/10.1016/j.jid.2021.04.019).
      Citation: Journal of Investigative Dermatology 141, 11 (2021)
      PubDate: 2021-11
      DOI: 10.1016/j.jid.2021.08.396
      Issue No: Vol. 141, No. 11 (2021)
       
  • Clinical Snippets

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      First page: 2547
      Abstract: The antibiotic dapsone is used to treat the pemphigoid diseases epidermolysis bullosa acquisita and mucous membrane pemphigoid despite its modest effects and its uncertain mode of action. Employing antibody transfer mouse models to mimic these diseases, Murthy et al. found that dapsone attenuated antibody-induced neutrophil-mediated skin and mucosal inflammation in these mice via inhibition of neutrophil responses to fixed immune complexes and anaphylatoxin C5a. Specifically, dapsone affected the release of leukotriene B4, ROS, matrix metalloproteinase 9, and MPO in response to immune complex stimulation.
      Citation: Journal of Investigative Dermatology 141, 11 (2021)
      PubDate: 2021-11
      DOI: 10.1016/j.jid.2021.08.399
      Issue No: Vol. 141, No. 11 (2021)
       
  • Editors’ Picks

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      First page: 2548
      Abstract: Studies have linked environmental allergen sensitization in atopic dermatitis (AD) skin, which harbors barrier defects, and subsequent allergen-specific IgE production with the development of other allergic diseases. However, keratinocyte (KC) signals that directly cause B cells to induce IgE class switching and production in the context of AD and to develop subsequent IgE-mediated lung disease have not been described. Patrick et al. (2021) investigated this question in a mouse model of AD-like skin inflammation after exposure to epicutaneous Staphylococcus aureus because S. aureus is increased and often exacerbates skin inflammation in patients with AD.
      Citation: Journal of Investigative Dermatology 141, 11 (2021)
      PubDate: 2021-11
      DOI: 10.1016/j.jid.2021.09.001
      Issue No: Vol. 141, No. 11 (2021)
       
  • Research Techniques Made Simple: Skin-Targeted Drug and Vaccine Delivery
           Using Dissolvable Microneedle Arrays

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      Authors: Stephen C. Balmert; Zohreh Gholizadeh Ghozloujeh, Cara Donahue Carey, Oleg E. Akilov, Emrullah Korkmaz, Louis D. Falo
      Pages: 2549 - 2557.e1
      Abstract: Skin-targeted drug delivery is broadly employed for both local and systemic therapeutics and is an important tool for discovery efforts in cutaneous biology. Recently, emerging technologies support efforts toward skin-targeted biocargo delivery for local and systemic therapeutic benefit. Effective targeting of bioactive molecules, including large (molecular weight> 500 Da) or complex (hydrophilic and charged) molecules, to defined cutaneous microenvironments is intrinsically challenging owing to the protective barrier function of the skin.
      Citation: Journal of Investigative Dermatology 141, 11 (2021)
      PubDate: 2021-11
      DOI: 10.1016/j.jid.2021.07.177
      Issue No: Vol. 141, No. 11 (2021)
       
  • Down-Regulated Calcium-Sensing Receptor in Keratinocytes and Skin from
           Aged Mice and Humans Impairs Function

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      Authors: Wendy B. Bollag
      Pages: 2558 - 2561
      Abstract: The calcium-sensing receptor (CaSR) is important in the skin, contributing to several epidermal functions, including differentiation, water permeability barrier repair, and wound healing. Celli et al. (2021) show that CaSR levels are reduced in keratinocytes/skin from aged individuals, with resulting impairment of key functions. CaSR agonists can correct these defects, suggesting a possible therapy to combat aging-related delayed skin wound healing.
      Citation: Journal of Investigative Dermatology 141, 11 (2021)
      PubDate: 2021-11
      DOI: 10.1016/j.jid.2021.04.005
      Issue No: Vol. 141, No. 11 (2021)
       
  • Making Lemonade: Putting the Wisdom of the Genome to Work in Atopic
           Dermatitis

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      Authors: Zhaolin Zhang; James T. Elder
      Pages: 2561 - 2564
      Abstract: Getting from a GWAS hit to an actionable gene remains a challenge in complex disease genetics. In a new article of the Journal of Investigative Dermatology, Sobczyk et al. (2021) use a wide variety of genomic data to generate a prioritization algorithm to tackle this problem in atopic dermatitis, calling on the wisdom of the genome to generate promising results.
      Citation: Journal of Investigative Dermatology 141, 11 (2021)
      PubDate: 2021-11
      DOI: 10.1016/j.jid.2021.05.027
      Issue No: Vol. 141, No. 11 (2021)
       
  • Treating Psoriasis with a Light Touch

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      Authors: Makoto Sugaya
      Pages: 2564 - 2566
      Abstract: Although several anticytokine antibodies and inhibitors are available for the treatment of psoriasis, more effective or better-tolerated alternatives would be of interest. In their article in the Journal of Investigative Dermatology, Michiels et al. (2021) propose a new strategy that targets an alternative activation pathway of the IL-22 receptor to attenuate murine psoriasis-like skin inflammation without affecting IL-22‒dependent barrier defense in the gut.
      Citation: Journal of Investigative Dermatology 141, 11 (2021)
      PubDate: 2021-11
      DOI: 10.1016/j.jid.2021.05.019
      Issue No: Vol. 141, No. 11 (2021)
       
  • A Possible Role for PAI-1 Blockade in Melanoma Immunotherapy

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      Authors: Mario Del Rosso; Gabriella Fibbi, Anna Laurenzana, Francesca Margheri, Anastasia Chillà
      Pages: 2566 - 2568
      Abstract: In their new article in the Journal of Investigative Dermatology, Tseng et al. (2021) confirm that the sensitivity of melanoma cells to anti‒PD-L1 checkpoint inhibitor therapy is correlated with high PD-L1 surface expression. By blocking PD-L1 membrane clearing, controlled by LRP1 and PAI-1, the expression of high-cell-surface levels of PD-L1 was maintained.
      Citation: Journal of Investigative Dermatology 141, 11 (2021)
      PubDate: 2021-11
      DOI: 10.1016/j.jid.2021.05.004
      Issue No: Vol. 141, No. 11 (2021)
       
  • High-plex spatial RNA profiling reveals cell type-specific biomarker
           expression during melanoma development

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      Authors: Maija Kiuru; Michelle A. Kriner, Samantha Wong, Guannan Zhu, Jessica R. Terrell, Qian Li, Margaret Hoang, Joseph Beechem, John D. McPherson
      Abstract: Early diagnosis of melanoma is critical for improved survival. However, biomarkers of early melanoma evolution and their origin within the tumor and its microenvironment, including the keratinocytes, are poorly defined. To address this, we used spatial transcript profiling that maintains the morphological tumor context to measure expression of>1,000 RNAs in situ in patient-derived formalin-fixed, paraffin-embedded tissue sections in primary melanoma and melanocytic nevi. We profiled 134 200μm-diameter regions of interest enriched in melanocytes, neighboring keratinocytes or immune cells.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-23
      DOI: 10.1016/j.jid.2021.06.041
       
  • NICOTINAMIDE EXERTS A PROTECTIVE EFFECT FROM UV-INDUCED STRESS DAMAGES ON
           HUMAN PRIMARY KERATINOCYTES FROM CANCERIZATION FIELD.

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      Authors: Lara Camillo; Laura C. Gironi, Elisa Zavattaro, Elia Esposto, Paola Savoia
      Abstract: Ultraviolet B (UVB) radiation directly damages DNA, increases reactive oxygen species (ROS) and nitric oxide (NO) release, and promotes inflammation leading to genomic instability and cell death. Nicotinamide (NAM) is the precursor of NAD, essential for cell energy production and DNA damage repair. NAM protects HaCat cells from UV-induced impairment; however, little is known about its effects on human primary keratinocytes (HPKs) and those isolated from field cancerization (FC-HPKs). We examined the role of NAM against UV-induced oxidative stress damages in FC-HPKs, isolated from precancerous lesions and skin cancers, and in normal epidermal keratinocytes (NHEK).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-22
       
  • Repurposing melanoma chemotherapy to activate inflammasomes in treatment
           of BRAF/MAPK inhibitor resistant melanoma

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      Authors: Farzana Ahmed; Hsin-Yi Tseng, Antonio Ahn, Dilini Gunatilake, Sara Alavi, Michael Eccles, Helen Rizos, Stuart Gallagher, Jessamy Tiffen, Peter Hersey, Abdullah Al Emran
      Abstract: The development of resistance to treatments of melanoma is commonly associated with upregulation of the MAPK pathway and development of an undifferentiated state. Prior studies have suggested that melanoma with these resistance characteristics may be susceptible to innate death mechanisms such as pyroptosis triggered by activation of inflammasomes. In the present studies we have taken cell lines from patients before and after development of resistance to BRAF V600 inhibitors and exposed the resistant melanoma to temozolomide (a commonly used chemotherapy) with and without chloroquine to inhibit autophagy.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-22
      DOI: 10.1016/j.jid.2021.09.030
       
  • Statin Use and Skin Cancer Risk: A Prospective Cohort Study

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      Authors: Marie Al Rahmoun; Reza Ghiasvand, Manon Cairat, Yahya Mahamat-Saleh, Iris Cervenka, Gianluca Severi, Marie-Christine Boutron-Ruault, Trude Eid Robsahm, Marina Kvaskoff, Agnès Fournier
      Abstract: Epidemiological studies on statin use in relation to skin cancer risk are scarce and yielded conflicting results. We explored this association in E3N, a prospective cohort of French women born in 1925-1950. Health and lifestyle data were self-reported biennially and matched with drug reimbursement data allowing to identify participants’ statin use since 2004. Multivariable cause-specific hazards regression models adjusted for skin cancer risk factors estimated hazard ratios (HRs) with 95% confidence intervals (CIs).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-22
       
  • CLASSIFICATION OF BASAL CELL CARCINOMA IN EX VIVO CONFOCAL MICROSCOPY
           IMAGES FROM FRESHLY EXCISED TISSUES USING A DEEP LEARNING ALGORITHM

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      Authors: Mercedes Sendín-Martín; Manuel Lara-Caro, Ucalene Harris, Matthew Moronta, Anthony Rossi, Erica Lee, Chih-Shan Jason Chen, Kishwer Nehal, Julián Conejo-Mir Sánchez, José-Juan Pereyra-Rodríguez, Manu Jain
      Abstract: Ex vivo confocal microscopy (EVCM) generates digitally colored purple-pink images similar to H&E, without time-consuming tissue processing. It can be used during Mohs surgery for rapid detection of basal cell carcinoma (BCC); however, reading EVCM images requires specialized training. An automated approach using a Deep Learning algorithm to BCC detection in EVCM images can aid in diagnosis. 40 BCCs and 28 negative (“not-BCC”) samples were collected at Memorial Sloan Kettering Cancer Center to create three training datasets: 1) EVCM image dataset (663 images), 2) H&E image dataset (516 images), and 3) a combination of the two datasets.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-22
      DOI: 10.1016/j.jid.2021.09.029
       
  • Regulation of 5-hydroxymethylcytosine by TET2 contributes to Squamous Cell
           Carcinoma tumorigenesis

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      Authors: Rafik Boudra; Yvon Woappi, Diana Wang, Shuyun Xu, Michael Wells, Chrysalyne D. Schmults, Christine G. Lian, Matthew R. Ramsey
      Abstract: DNA methylation is a key regulatory event controlling a variety of physiological processes and can have dramatic effects on gene transcription. Methylated Cytosine (5mC) can be oxidized by the TET family of enzymes to 5-hydroxymethylcytosine (5-hmC), a key intermediate in the de-methylation cycle, and 5-hmC levels are reduced in malignancies such as AML and melanoma. We constructed a tissue microarray of human cutaneous Squamous Cell Carcinoma (SCC) tumors and found a global reduction in 5-hmC levels compared to adjacent skin.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-22
      DOI: 10.1016/j.jid.2021.09.026
       
  • Soluble DC-HIL/Gpnmb Modulates T-lymphocyte Extravasation to Inflamed Skin

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      Authors: Vijay Ramani; Jin-Sung Chung, Kiyoshi Ariizumi, Ponciano D. Cruz
      Abstract: Previously we discovered antigen-presenting cells (APC) to express the DC-HIL receptor and to secrete its soluble form (sDC-HIL), both of which bind to syndecan-4 (SD4) on T-cells and endothelial cells (EC), with the former binding attenuating T-cell function and the latter binding promoting angiogenesis. Herein we examined effects of sDC-HIL binding to EC on T-cell extravasation using an allergic contact dermatitis model in mice. The hapten oxazolone applied to ear skin in sensitized mice upregulated cutaneous expression of sDC-HIL, which downregulated the allergic reaction by reducing transendothelial migration of T-cells, but not other immune cells (neutrophils and mast cells).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-22
       
  • Pulsed electric fields induce extracellular matrix remodeling through MMPs
           activation and decreased collagen production

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      Authors: Sara Gouarderes; Camille Ober, Layal Doumard, Jany Dandurand, Patricia Vicendo, Isabelle Fourquaux, Alexander Golberg, Valérie Samouillan, Laure Gibot
      Abstract: INTRODUCTION. The extracellular matrix (ECM) is a dynamic and complex mesh of structural proteins and carbohydrates that are essential for tissue development, structure, and functionality (Frantz et al. 2010). Impairment in its regulation, composition, biophysical properties and remodeling is observed in diseases such as cancers or fibrosis (Winkler et al. 2020). ECM components and the proteins that regulate ECM remodeling appear as promising therapeutic targets for human healthcare (Ivey et al.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-21
      DOI: 10.1016/j.jid.2021.09.025
       
  • Adipocyte-derived C1q-TNF-related Protein 3 Exhibits Anti-inflammatory
           effects via LAMP1-STAT3 axis in Psoriasis

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      Authors: Ke Xue; Shuai Shao, Hui Fang, Lirong Ma, Caixia Li, Zifan Lu, Gang Wang
      Abstract: Psoriasis is a systemic disease that is associated with metabolic disorders, which may attribute to the abnormal adipokines levels. However, the underlying mechanism is largely unknown. Here, we investigated the role of adipokine C1q-TNF-related protein-3 (CTRP3) in the pathogenesis of psoriasis and comorbidities. The circulating CTRP3 level in psoriasis patients was significantly lower than that in healthy controls and negatively correlated with metabolic risk factors. Rescuing CTRP3 level with glucagon-like peptide-1 receptor agonist, exendin-4, in diet-induced obese mice could alleviate its severer psoriatic symptoms in imiquimod (IMQ)-induced mouse model.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-20
      DOI: 10.1016/j.jid.2021.09.027
       
  • Vemurafenib drives EMT gene expression in BRAFi-resistant
           BRAFV600E/NRASQ61K melanoma enhancing tumor growth and metastasis in a
           bioluminescent murine model

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      Authors: Jana Jandova; Georg T. Wondrak
      Abstract: BRAF-inhibitor (BRAFi)-resistance compromises long term survivorship of malignant melanoma patients, and mutant NRAS is a major mediator of BRAFi-resistance. Here, employing phenotypic and transcriptomic analysis of isogenic melanoma cells that differ only by NRAS mutational status (BRAFi-sensitive A375-BRAFV600E/NRASQ61 versus BRAFi-resistant A375-BRAFV600E/NRASQ61K) we demonstrate that BRAFi (vemurafenib) treatment selectively targets BRAFV600E/NRASQ61K cells upregulating epithelial-to-mesenchymal transition (EMT) gene expression, paradoxically promoting invasiveness and metastasis in vitro and in vivo.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-20
       
  • A methylome and transcriptome analysis of normal human scar cells reveals
           a role for FOXF2 in scar maintenance

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      Authors: Andrew W. Stevenson; Phillip E. Melton, Eric.K. Moses, Hilary J. Wallace, Fiona M. Wood, Suzanne Rea, Patricia L. Danielsen, Mansour Alghamdi, Nicole Hortin, Julia Borowczyk, Zhenjun Deng, Mitali Manzur, Mark W. Fear
      Abstract: Scar is maintained for life and increases in size during periods of growth such as puberty. Epigenetic changes in fibroblasts after injury may underpin the maintenance and growth of scar. Here, we, combined methylome and transcriptome data from normotrophic mature scar and contralateral uninjured normal skin fibroblasts to identify potential regulators of scar maintenance. 219 significantly differentially expressed and 1199 significantly differentially methylated promoters were identified, of which there were 12 genes both significantly differentially methylated and expressed.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-20
      DOI: 10.1016/j.jid.2021.08.445
       
  • State of residency: microbial strain diversity in the skin

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      Authors: Heidi H. Kong; Julia Oh
      Abstract: Human skin hosts a diversity of microbiota. Advances in sequencing and analytical methods have increasingly illuminated the importance of the finest resolution in understanding the genetic diversity of the skin microbiota, highlighting strain-level differences and their functional implications. Such genetic diversity, which exists within-individual and is strongly individual-specific, underscores the difficulty in elucidating functionality. Integrated investigations of the microbial strain diversity via sequencing and culture-based approaches with host immunology and physiology will be critical in expanding our understanding of the roles of the skin microbiome.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-20
       
  • PLCγ1/PKCθ Downstream Signaling Controls Cutaneous T-Cell Lymphoma
           Development And Progression

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      Authors: N. García-Díaz; B. Casar, R. Alonso-Alonso, L. Quevedo, M. Rodríguez, F. Ruso-Julve, A. Esteve-Codina, M. Gut, A.A. Gru, M.C. González-Vela, I. Gut, J.L. Rodriguez-Peralto, I. Varela, P.L. Ortiz-Romero, M.A. Piris, J.P. Vaqué
      Abstract: Developing mechanistic rationales can improve the clinical management of cutaneous T-cell lymphomas (CTCL). There is considerable genetic and biological evidence of a malignant network of signaling mechanisms, highly influenced by deregulated TCR/PLCγ1 activity, controlling the biology of these lesions. In addition, activated STAT3 is associated with clinical progression, although the alterations responsible for this have not been fully elucidated. Here we studied PLCγ1-dependent mechanisms that can mediate STAT3 activation and control tumor growth and progression.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-20
      DOI: 10.1016/j.jid.2021.09.024
       
  • Oncogenic KIT Induces Replication stress and Confers Cell Cycle Checkpoint
           Vulnerability in Melanoma

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      Authors: Ching-Ni Njauw; Zhenyu Ji, Duc Minh Pham, Antoine Simoneau, Raj Kumar, Keith T. Flaherty, Lee Zou, Hensin Tsao
      Abstract: Acral and mucosal melanomas (AMM’s) arise from sun-protected sites, disproportionately impact darker-skinned individuals and exact a higher mortality than common types of cutaneous melanoma. Genetically, AMM’s harbor more alterations of KIT compared to typical CM’s. As KIT-mutated melanomas remain largely treatment resistant, we set out to create a faithful murine KIT-driven allograft model to define newer therapeutic strategies. Using the prevalent human KITK642E activating mutation, the murine mKITK641E cellular avatars show features of transformation in vitro and tumorigenic in immunocompetent C57BL/6J mice.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-20
      DOI: 10.1016/j.jid.2021.07.188
       
  • Particulate matter promotes melanin production via endoplasmic reticulum
           stress-mediated IRE1α signaling

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      Authors: Yuri Ahn; Eun Jung Lee, Enzhi Luo, Junjeong Choi, Ji Young Kim, Suho Kim, Se-Hwa Kim, Yu Jeong Bae, Sujin Park, Jinu Lee, Sang Ho Oh
      Abstract: Particulate matter (PM) is believed to be related to cardiovascular and respiratory diseases. The skin is also known to be affected by PM exposure as a result of skin barrier dysfunction, cutaneous inflammation, and apoptotic cell death. Epidemiological studies have suggested that PM is related to pigment spots. Recently, diesel exhaust particles are reported to cause a tanning response mediated by oxidative stress. However, the direct effects of PM on melanogenesis and related mechanisms have not yet been clarified.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-19
      DOI: 10.1016/j.jid.2021.08.444
       
  • Pathogenic autoantibody derived from Treg-deficient scurfy mice targets
           

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      Authors: Elisabeth Vicari; Stefanie Haeberle, Vanessa Bolduan, Torben Ramcke, Artem Vorobyev, Stephanie Goletz, Hiroaki Iwata, Ralf J. Ludwig, Enno Schmidt, Alexander H. Enk, Eva N. Hadaschik
      Abstract: Autoimmune blistering diseases (AIBD) are severe human autoimmune diseases affecting the skin and mucous membranes (Witte et al., 2018). AIBD patients develop pathogenic autoantibodies targeting structural skin proteins and causing intraepidermal blisters to form as in pemphigus vulgaris (PV) or at the basement membrane zone (BMZ) as in pemphigoid diseases (Schmidt and Zillikens, 2011). For many AIBD, the events following autoantibody binding have been elucidated. However, early events in the pathogenic cascade leading to autoantibody production are still not fully understood.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-19
      DOI: 10.1016/j.jid.2021.08.441
       
  • Read-through for nonsense mutations in type XVII collagen deficient
           junctional epidermolysis bullosa

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      Authors: Cristina Has; Saliha Beyza Sayar, Shuangshuang Zheng, Esteban Chacón-Solano, Irina Condrat, Ayushi Yadav, Michel Roberge, Fernando Larcher Laguzzi
      Abstract: Junctional epidermolysis bullosa (JEB) is caused by mutations in genes encoding adhesion proteins, such as laminin 332, type XVII collagen (C17), integrin α6β4 or integrin α3. Absence of C17 leads to intermediate JEB that manifests with generalized skin blisters, chronic wounds, hair loss, nail loss or dystrophy, and enamel hypoplasia (Has et al., 2020). There is no cure, and no experimental therapy has been developed for JEB with C17 deficiency (Prodinger et al., 2020). About 20% of the COL17A1 pathogenic variants are nonsense mutations leading to absence of C17.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-18
      DOI: 10.1016/j.jid.2021.09.018
       
  • Positive Attributes of Anti-TERT CD4 T-Helper Type 1 Immune Responses in
           Melanoma

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      Authors: Eduardo Nagore; Amaya Virós, Rajiv Kumar
      Abstract: Nardin et al's (2021) study on melanoma reports anti-TERT CD4 T helper type (Th) 1 responses in more than half of patients. Besides indicating a trend for improved survival, increased anti-TERT CD4 Th1 responses predicted better outcomes for patients treated with immune checkpoint inhibitors. Thus, harnessing systemic anti-TERT CD4 Th1 responses together with tumor-specific elevation of telomerase can potentially open new avenues for biomarkers and treatment in melanoma.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-16
      DOI: 10.1016/j.jid.2021.09.005
       
  • Interactions of the neuro-immune-stromal triad in itch

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      Authors: Pang-Yen Tseng; Mark A. Hoon
      Abstract: This prospective focuses on recent advances in understanding of the mechanisms involved in itch signaling in the skin and how these new findings fit into the wider picture of the expression of itch mediators and their receptors in the dermal layer. Since, at present, studies mostly concentrate on single cellular compartments (e.g. neural alone), we suggest that they may miss important interactions with other compartments. Therefore, we propose that studies, in order to fully appreciate pruritus, should consider (e.g., by using transcriptomic information) signal transmission within the entire neuro-immune-stromal triad.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-15
      DOI: 10.1016/j.jid.2021.08.443
       
  • Circuit Mechanisms of Itch in the Brain

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      Authors: Di Mu; Yan-Gang Sun
      Abstract: Itch is an unpleasant somatic sensation with the desire to scratch, and it consists of sensory, affective, and motivational components. Acute itch serves as a critical protective mechanism, as itch-evoked scratching response will help to remove harmful substances invading the skin. Recently, exciting progress has been made in deciphering the mechanisms of itch at both the peripheral and central nervous system levels. Key neuronal subtypes and circuits have been revealed for ascending transmission and the descending modulation of itch.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-15
      DOI: 10.1016/j.jid.2021.09.022
       
  • Examining Evidence For A Causal Association Between Telomere Length &
           Nevus Count

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      Authors: Nathan Ingold; Jean Claude Dusingize, Rachel E. Neale, Catherine M. Olsen, David C. Whiteman, David L. Duffy, Stuart MacGregor, Matthew H. Law
      Abstract: Nevi (moles) are collections of non-dendritic melanocytes in the skin that form darkly pigmented spots. Nevi-prone individuals are at a higher risk of melanoma. Mean telomere length is a highly heritable trait that has been associated with many diseases, including melanoma (Butt et al., 2010; Han et al., 2009; Rachakonda et al., 2018). Observational studies have found an association between shorter telomere length and reduced nevus count, while others report null findings (Bataille et al., 2007; Han et al., 2009; Li et al., 2016).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-14
      DOI: 10.1016/j.jid.2021.09.021
       
  • Chlamydia trachomatis stimulation enhances HIV-1 susceptibility via the
           modulation of a member of the macrophage inflammatory proteins

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      Authors: Emmanuel Enoch Dzakah; Jiacong Zhao, Liuyan Wang, Farooq Rashid, Ru Xu, Ligang Yang, Zhengwei Wan, Liping Huang, Haiying Wang, Shuyi Chen, Wujian Ke, Foster Kyei, Kai Deng, Shixing Tang
      Abstract: Sexually transmitted infections (STI) such as Chlamydia trachomatis (CT) can enhance human immunodeficiency virus type one (HIV-1) infection. However, the molecular mechanisms modulating the enhancement of HIV-1 infectivity and replication during HIV-1/STIs coinfection remain elusive. In this study, we performed an ex vivo infection of HIV-1 in peripheral blood mononuclear cells (PBMCs) of C. trachomatis-infected patients and observed a significant increase in HIV-1 p24 levels as compared to cells from healthy donors.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-14
      DOI: 10.1016/j.jid.2021.09.020
       
  • Preclinical evaluation of LVR01 attenuated Salmonella as neoadjuvant
           intralesional therapy in combination with chemotherapy for melanoma
           treatment.

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      Authors: Sofía Chilibroste; Amy Mónaco, María C. Plata, Magdalena Vola, Caroline I. Agorio, José A. Chabalgoity, María Moreno
      Abstract: Treatment of malignant melanoma has improved in the last few years, due to early detection and new therapeutic options. Still, management of advanced disease remains a challenge, since it requires a systemic treatment. In such cases, dacarbazine (DTIC)-based chemotherapy has been widely used, despite low efficacy. Neoadjuvant therapies emerge as alternative options that could help chemotherapy to achieve increased benefit. In this work, we evaluate LVR01, an attenuated Salmonella enterica serovar Typhimurium, as neoadjuvant intralesional therapy in combination with DTIC in a preclinical melanoma model.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-14
      DOI: 10.1016/j.jid.2021.08.442
       
  • Phospholipase Cγ2 is essential for experimental models of
           epidermolysis bullosa acquisita

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      Authors: Kata P. Szilveszter; Simon Vikár, Ádám I. Horváth, Zsuzsanna Helyes, Miklós Sárdy, Attila Mócsai
      Abstract: Phospholipase Cγ2 (PLCγ2) mediates tyrosine kinase-coupled receptor signaling in various hematopoietic lineages. Although PLCγ2 has been implicated in certain human and mouse inflammatory disorders, its contribution to autoimmune and inflammatory skin diseases is poorly understood. Here we tested the role of PLCγ2 in a mouse model of epidermolysis bullosa acquisita triggered by antibodies against type VII collagen (C7), a component of the dermo-epidermal junction. PLCγ2-deficient (Plcg2–/–) mice and bone marrow chimeras with a Plcg2–/– hematopoietic system were completely protected from signs of anti-C7-induced skin disease including skin erosions, dermal-epidermal separation and inflammation, despite normal circulating levels and skin deposition of anti-C7 antibodies.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-14
      DOI: 10.1016/j.jid.2021.09.019
       
  • Vitiligo skin T cells are prone to produce type 1- and type 2-cytokines to
           induce melanocyte dysfunction and epidermal inflammatory response through
           JAK signaling

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      Authors: Christina Martins; Laure Migayron, Claire Drullion, Clément Jacquemin, Fabienne Lucchese, Jérôme Rambert, Ribal Merhi, Pauline Michon, Alain Taieb, Hamid-Reza Rezvani, Emanuele de Rinaldis, Julien Seneschal, Katia Boniface
      Abstract: Vitiligo is a T cell-mediated inflammatory skin disorder characterized by the loss of epidermal melanocytes. However, the contribution of melanocytes to the physiopathology of the disease in response to the T cell microenvironment remains unclear. Here, using NanoString technology and multiplex ELISA, we show that active vitiligo perilesional skin is characterized by prominent type 1 and 2 associated immune responses. The vitiligo skin T cell secretome downregulated melanocyte function and adhesion, while increasing melanocyte mitochondrial metabolism and expression of inflammatory cytokines and chemokines by epidermal cells.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-13
      DOI: 10.1016/j.jid.2021.09.015
       
  • Genome-wide association study identifies multiple genetic loci for skin
           color in Korean women

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      Authors: Jung Yeon Seo; Seung Won You, Joong-Gon Shin, Yunkwan Kim, Sun Gyoo Park, Hong-Hee Won, Nae Gyu Kang
      Abstract: Human skin color is largely determined by genetic factors. Recent genome-wide association studies (GWAS) have reported several genetic variants associated with skin color, mostly in European and African populations. In this study, we performed GWAS in 17,019 Korean women to identify genetic variants associated with facial skin color, quantitatively measured as CIELAB color index. We identified variants in three, one, and six genomic loci associated with facial skin color index L*, a*, and b* values, respectively, and replicated the associations (combined analysis P-value < 5.0 × 10-8).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-10
      DOI: 10.1016/j.jid.2021.08.440
       
  • IL-6R/STAT3-signaling in keratinocytes rather than T cells induces
           psoriasis-like dermatitis in mice

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      Authors: Advaitaa Ravipati; Sabrina Nolan, Martin Alphonse, Dustin Dikeman, Christine Youn, Yu Wang, Nicholas Orlando, Garrett Patrick, Steven Lee, Roger V. Ortines, Haiyun Liu, Robert J. Miller, Carly A. Dillen, Mark Marchitto, S. Sarah Cai, Lloyd S. Miller, Nathan K. Archer
      Abstract: STAT3 is important for psoriasis pathogenesis as STAT3-signaling downstream of IL-6, IL-21, IL-22 and IL-23 contributes to Th17 cell development and keratinocyte STAT3 expression in transgenic mice (K14-Stat3C mice) develop psoriasis-like dermatitis. Herein, the relative contribution of STAT3-signaling in keratinocytes versus T cells was evaluated in the imiquimod model of psoriasis-like dermatitis. Mice with STAT3 inducible deletion in keratinocytes (K5-STAT3–/– mice) had decreased psoriasis-like dermatitis and epidermal phosphorylation of STAT3 (pSTAT3) compared with wt mice, whereas mice with constitutive deletion of STAT3 in all T cells were like wt mice.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-06
      DOI: 10.1016/j.jid.2021.09.012
       
  • TEMPORARY REMOVAL: Society for Investigative Dermatology 2020 Board of
           Directors Meeting Minutes

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      Authors: Jim Rumsey
      Abstract: The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated.The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-05
      DOI: 10.1016/j.jid.2021.09.011
       
  • Systemic collagen VII replacement therapy for advanced recessive
           dystrophic epidermolysis bullosa

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      Authors: Christine Gretzmeier; Didier Pin, Johannes S. Kern, Mei Chen, David T. Woodley, Leena Bruckner-Tuderman, Mark P. de Souza, Alexander Nyström
      Abstract: Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin blistering disease associated with progressive multi-organ fibrosis. RDEB is caused by biallelic mutations in COL7A1 encoding the extracellular matrix protein collagen VII (C7), which is necessary for epidermal-dermal adherence. C7 is not simply a structural protein but also has multiple functions, including regulation of TGFβ bioavailability and the inhibition of skin scarring. Intravenous (IV) administration of recombinant C7 (rC7) rescues C7 deficient mice from neonatal lethality.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-01
      DOI: 10.1016/j.jid.2021.09.008
       
  • TSST-1+ Staphylococcus aureus in Bullous pemphigoid

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      Authors: Kelly N. Messingham; Michael P. Cahill, Samuel H. Kilgore, Ananya Munjal, Patrick M. Schlievert, Janet A. Fairley
      Abstract: A potential role of S. aureus in BP was explored by examining the colonization rate in patients with new-onset disease, compared to age- and sex-matched controls. S. aureus colonization was observed in 85% of BP lesions; 3-6-fold higher than the nares or unaffected skin from the same patients (p≤0.003) and 6-fold higher than nares or skin of controls (p≤0.0015). Furthermore, 96% of the lesional isolates produced the toxic shock syndrome toxin-1 (TSST-1) superantigen and most of these additionally exhibited homogeneous expression of the enterotoxin gene cluster (EGC) toxins.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-10-01
      DOI: 10.1016/j.jid.2021.08.438
       
  • Autoantibodies present in Hidradenitis suppurativa correlate with disease
           severity and promote release of proinflammatory cytokines in macrophages

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      Authors: Carmelo Carmona-Rivera; Liam J. O’Neil, Eduardo Patino-Martinez, William D. Shipman, Chengsong Zhu, Quan-Zhen Li, Michelle L. Kerns, Leandra A. Barnes, Julie A. Caffrey, Sewon Kang, Mariana J. Kaplan, Ginette A. Okoye, Angel S. Byrd
      Abstract: Hidradenitis suppurativa (HS), also known as acne inversa, is a debilitating inflammatory skin disorder that is characterized by nodules that lead to the development of connected tunnels and scars as it progresses from Hurley stage I to III. HS has been associated with several autoimmune diseases, including inflammatory bowel disease (IBD) and spondyloarthritis. We previously reported dysregulation of humoral immune responses in HS, characterized by elevated serum total IgG, B cell activation and antibodies recognizing citrullinated proteins.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-30
      DOI: 10.1016/j.jid.2021.07.187
       
  • Activation of fibroblasts in skin cancer

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      Authors: Lisette Van Hove; Esther Hoste
      Abstract: Fibroblasts have emerged as a dominant component of the tumour microenvironment, but despite the surging interest in the activation of fibroblasts and their role in cancer, they remain an elusive and complex cell-type. In this perspective, we discuss the phenotypic plasticity of cancer-associated fibroblasts in melanoma and non-melanoma skin cancer identified by genome-wide transcriptomic studies and focus on the molecular pathways underlying their activation. These studies reveal distinct fibroblast activation profiles depending on tumour type and stage.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-29
      DOI: 10.1016/j.jid.2021.09.010
       
  • Functional Assessment of Missense Variants in the ABCC6 gene Implicated in
           Pseudoxanthoma Elasticum, a Heritable Ectopic Mineralization Disorder

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      Authors: Luke Kowal; Jianhe Huang, Hongbin Luo, Jagmohan Singh, Adam E. Snook, Jouni Uitto, Qiaoli Li
      Abstract: Pseudoxanthoma elasticum (PXE), a heritable multi-system ectopic mineralization disorder, is caused by inactivating mutations in the ABCC6 gene. The encoded protein ABCC6, a transmembrane transporter, has a specialized efflux function in hepatocytes by contributing to plasma levels of PPi, a potent inhibitor of mineralization in soft connective tissues. Reduced plasma PPi levels underlie the ectopic mineralization in PXE. In this study, we characterized the pathogenicity of three human ABCC6 missense variants using an adenovirus-mediated liver-specific ABCC6 transgene expression system in an Abcc6-/- mouse model of PXE.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-28
      DOI: 10.1016/j.jid.2021.08.435
       
  • Anti-melanoma effects of concomitant inhibition of SIRT1 and SIRT3 in
           BrafV600E/PtenNULL mice

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      Authors: Gagan Chhabra; Chandra K. Singh, Glorimar Guzmán-Pérez, Mary A. Ndiaye, Kenneth A. Iczkowski, Nihal Ahmad
      Abstract: Novel therapeutic strategies are required for the effective and lasting treatment of metastatic melanoma, one of the deadliest skin malignancies. In this study, we determined the anti-melanoma efficacy of 4′-bromo-resveratrol (4′-BR), which is a small molecule dual inhibitor of SIRT1 and SIRT3 in a BrafV600E/PtenNULL mouse model that recapitulates human disease, including metastases. Tumors were induced by topical application of 4-hydroxy-tamoxifen on shaved backs of 10-week-old mice, and the effects of 4′-BR (5-30 mg/kg b.wt.; intraperitoneally; 3d/week for 5 weeks) were assessed on melanoma development and progression.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-28
      DOI: 10.1016/j.jid.2021.08.434
       
  • PHLDA3 is an important downstream mediator of p53 in squamous cell
           carcinogenesis

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      Authors: Megumi Saito; Akane Sada, Masaki Fukuyo, Kiyono Aoki, Kazuhiro Okumura, Yuko Tabata, Yu Chen, Atsushi Kaneda, Yuichi Wakabayashi, Rieko Ohki
      Abstract: Squamous cell carcinomas (SCCs) are one of the most frequent solid cancer types in humans and are derived from stratified epithelial cells found in various organs. SCCs derived from various organs share common important properties including genomic abnormalities in the tumor suppressor gene p53. There is a carcinogen-induced mouse model of SCC which produces benign papilloma, some of which progress to advanced carcinoma and metastatic SCCs. These SCCs undergo key genetic alterations that are conserved between human and mice, including alterations in the genomic p53 sequence, and is therefore an ideal system to study the mechanisms of SCC tumorigenesis.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-26
      DOI: 10.1016/j.jid.2021.09.007
       
  • EZH2 inhibitor enhances the STING agonist-induced antitumor immunity in
           melanoma

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      Authors: Tianxiao Xu; Jie Dai, Lirui Tang, Lu Yang, Lu Si, Xinan Sheng, Chuanliang Cui, Zhihong Chi, Yan Kong, Jun Guo
      Abstract: STING agonists are a new class of drugs for cancer immunotherapy that activate both innate and adaptive antitumor immunity. Recently, multiple clinical trials of STING agonists have been conducted in hematological malignancies and solid tumors. However, STING is commonly suppressed in melanoma via mechanisms that remain unclear. We found that STING expression was epigenetically suppressed by H3K27me3 in melanoma, and EZH2 inhibitor could induce an H3K27 shift from trimethylation to acetylation, resulting in increased expression of STING.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-24
      DOI: 10.1016/j.jid.2021.08.437
       
  • A genome-wide scan on individual typology angle found variants at SLC24A2
           associated with skin color variation in Chinese populations

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      Authors: Fudi Wang; Qi Luo, Yan Chen, Yu Liu, Ke Xu, Kaustubh Adhikari, Xiyang Cai, Jialin Liu, Yi Li, Xuyang Liu, Luis-Miguel Ramirez-Aristeguieta, Ziyu Yuan, Yong Zhou, Fu-Feng Li, Binghua Jiang, Li Jin, Andres Ruiz-Linares, Zhaohui Yang, Fan Liu, Sijia Wang
      Abstract: Skin pigmentation functions as a shield to prevent UV damage on the DNA of epidermal cells. A good number of genome-wide association studies (GWASs) on skin color variation or skin photosensitivity have been conducted that discovered a large number of associated loci (Ganguly et al., 2019). Polymorphisms/mutations at these loci have been used to molecular type skin color for individuals from different continental groups (Chen et al., 2020), and have been associated with various forms of Albinism (Marcon and Maia, 2019), loss of photoprotection, and increased rates of photoaging (Liu et al., 2016).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-24
      DOI: 10.1016/j.jid.2021.07.186
       
  • Nailfold Microvascular Imaging by Dynamic Optical Coherence Tomography in
           Systemic Sclerosis: a Case-Controlled Pilot Study

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      Authors: Giuseppina Abignano; Lorraine Green, Sookhoe Eng, Paul Emery, Francesco Del Galdo
      Abstract: In systemic sclerosis (SSc) outcome measures of skin microvasculopathy are needed for both clinical trials and practice. Aim of this study was to determine whether dynamic-optical coherence tomography (D-OCT) is able to provide information on microvasculopathy compared to the current gold-standard, nailfold videocapillaroscopy (NVC), in SSc patients. This case-controlled study included: 1) forty SSc patients, classified by NVC pattern in 4 age- and sex-matched groups (normal/non-specific, early, active, late); 2) a fifth group of ten age- and sex-matched healthy controls (HC).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-24
      DOI: 10.1016/j.jid.2021.08.436
       
  • TRPC3 Antagonizes Pruritus in A Mouse Contact Dermatitis Model

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      Authors: Katherine Beattie; Haowu Jiang, Mayank Gautam, Mary K. MacVittie, Barbara Miller, Minghong Ma, Qin Liu, Wenqin Luo
      Abstract: Contact dermatitis (CD), including allergic and irritant CD, are common dermatological diseases and characterized by an erythematous rash and severe itch. In this study, we investigated the function of TRPC3, a canonical TRP channel highly expressed in type 1 non-peptidergic (NP1) nociceptive primary afferents and other cell types, in a mouse CD model. Though TrpC3 null mice had little deficits in acute somatosensation, they showed significantly increased scratching with CD. In addition, TrpC3 null mice displayed no differences in mechanic and thermal hypersensitivity in an inflammatory pain model, suggesting that this channel preferentially functions to antagonize CD-induced itch.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-24
      DOI: 10.1016/j.jid.2021.08.433
       
  • Keratinocytes Counteract UVB-Induced Immunosuppression in Mice Via HIF-1a
           Signaling

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      Authors: Sonja Faßbender; Kevin Sondenheimer, Marc Majora, Jennifer Schindler, Friederike V. Opitz, Marius Pollet, Thomas Haarmann-Stemmann, Jean Krutmann, Heike Weighardt
      Abstract: The transcription factor Hypoxia-Inducible Factor-1alpha (HIF-1a) regulates cellular metabolism under hypoxia but also immune responses and UVB-induced skin reactions. In keratinocytes, HIF-1a is an environmental sensor orchestrating the adaptation to environmental changes. Here, we investigated the role of HIF-1a in keratinocytes for skin reactions to acute and chronic UVB exposure in mice.The function of HIF-1a in keratinocytes under UVB exposure was analyzed in conditional keratinocyte-specific HIF-1a-KO (in short “cKO”) mice.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-24
      DOI: 10.1016/j.jid.2021.07.185
       
  • Exclusive expression of MyD88 on dendritic cells is sufficient to induce
           protection against experimental leishmaniasis

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      Authors: Susanna Lopez Kostka; Kordula Kautz-Neu, Nir Yogev, Dominika Lukas, Bernhard Holzmann, Ari Waisman, Björn E. Clausen, Esther von Stebut
      Abstract: Leishmania parasites, endemic in (sub-)tropical regions, cause a neglected tropical disease affecting ∼12 million cases worldwide. The spectrum of pathologies ranges from cutaneous leishmaniasis to progressive fatal visceral disease. Both in humans and mice, healing is associated with successful development of IFNγ-producing Th1/Tc1 cells, whereas Th2-, Th17- and Treg-predominant responses are associated with progression and/or non-healing lesions (Sacks & Noben-Trauth, 2002; Kautz-Neu et al., 2011).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-24
      DOI: 10.1016/j.jid.2021.07.184
       
  • Ode to Salt: Commentary on “Skin Sodium Accumulates in Psoriasis and
           Reflects Disease Severity”

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      Authors: Theodora M. Mauro
      Abstract: “Skin Sodium Accumulates in Psoriasis and Reflects Disease Severity” (Maifeld et al., 2021) showed that skin sodium ion (Na+) is increased in patients with a PASI> 5. Na+ concentration as well as its content were increased in these patients, supporting the proposed mechanism that increased Na+ concentrations enhance IL-17 expression from CD4+ cells. These data initially were generated using a noninvasive technique, sodium (23Na) magnetic resonance imaging, and then were verified using 23Na spectroscopy and atomic absorption spectrometry in ashed-skin biopsies in humans and also using mouse models of psoriasis.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-24
      DOI: 10.1016/j.jid.2021.08.401
       
  • IFN-1s: Sentinels Shaping Distinct Immune Responses in Skin

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      Authors: Natalie Garzorz-Stark; Kilian Eyerich
      Abstract: IFN-1s are early sentinels of potential danger in skin. Two interconnected axes exist: plasmacytoid dendritic cells (DCs) secreting IFN-α in response to single strand RNA or DNA and keratinocytes secreting IFN-κ after stimulation with double strand RNA or other IFNs. Both IFN-α and IFN-κ induce macrophages and DC subpopulations to secrete master regulators of cytotoxicity or wound healing, the latter related to psoriasis pathogenesis.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-22
      DOI: 10.1016/j.jid.2021.07.161
       
  • Targeting the FcRn: A Novel Approach to the Treatment of Pemphigus

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      Authors: Caroline A. Nelson; Mary M. Tomayko
      Abstract: Pemphigus is a debilitating autoimmune blistering disorder mediated by IgG autoantibodies to desmosomal cadherins that requires novel steroid-sparing therapies. In this phase 1b/2 trial reported by Werth et al. (2021), the FcRn inhibitor ALXN1840 induced rapid and sustained clinical improvement in patients with chronic, active, refractory pemphigus. FcRn inhibition is a promising new approach to the treatment of pemphigus and other autoantibody-mediated autoimmune disorders.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-22
      DOI: 10.1016/j.jid.2021.06.035
       
  • Histone Deacetylases in the Control of Epidermal Homeostasis: From
           Chromatin Biology toward Therapy

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      Authors: Vladimir A. Botchkarev; Andrey A. Sharov
      Abstract: Histone deacetylases (HDACs) induce gene repression and modify the activity of nonhistone proteins. In a new article in the Journal of Investigative Dermatology, Zhu et al. (2021) demonstrate essential roles for HDAC1/2 in maintaining keratinocyte proliferation and survival in adult epidermis and basal cell carcinoma, thus providing a rationale for using HDAC inhibitors for the treatment of hyperproliferative and neoplastic skin disorders.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-22
      DOI: 10.1016/j.jid.2021.06.021
       
  • Ironing-Out the Details: New Strategies for Combining Ferroptosis
           Inhibitors with Immunotherapy in Melanoma

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      Authors: Michael F. Emmons; Keiran S.M. Smalley
      Abstract: Escape from ferroptosis is an important determinant of metastasis and immune evasion in melanoma. In a new article of the Journal of Investigative Dermatology, Wang et al. (2021) identify the CAMKK2‒adenosine monophosphate–activated protein kinase‒NRF2 signaling axis as a negative regulator of ferroptosis and showed that inhibiting CAMKK2 increases the efficacy of anti–PD-1 therapy. These findings offer new opportunities for the development of ferroptosis-inducing therapies to use in combination with immune checkpoint agents.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-22
      DOI: 10.1016/j.jid.2021.06.014
       
  • Impaired Autophagy in Psoriasis and Atopic Dermatitis: A New Therapeutic
           Target'

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      Authors: Stephan Hailfinger; Klaus Schulze-Osthoff
      Abstract: Dysfunctional autophagy is linked to various diseases, including psoriasis and atopic dermatitis. Recent evidence suggests that exposure of keratinocytes to TNF-α results in impaired autophagy and lysosomal function. The skin of patients with psoriasis and atopic dermatitis reveals a decreased expression of lysosomal cathepsins. Impaired autophagy is presumably involved in inflammation and disturbed keratinocyte differentiation, whereas stimulating autophagy might be a treatment option in inflammatory skin disease.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-22
      DOI: 10.1016/j.jid.2021.06.006
       
  • Cathelicidin LL-37 Ignites Primed NLRP3 Inflammasomes in Rosacea

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      Authors: David O. Croitoru; Vincent Piguet
      Abstract: Microbes and commensal mites contribute to the development of inflammation and neurovascular dysregulation in rosacea. Cathelicidin family proteins are epithelial antimicrobial peptides expressed in higher-order mammals. In humans, mature LL-37 is cleaved from its precursor in response to microbial infection, UV light, and injury. In their new article in the Journal of Investigative Dermatology, Yoon et al. expand on existing evidence supporting LL-37 proinflammatory activity in lipopolysaccharide (LPS)- and UV-primed models of rosacea.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-22
      DOI: 10.1016/j.jid.2021.04.024
       
  • MFN2 Stabilization: A Bridge for Endoplasmic Reticulum Stress Sensitivity
           in Melanoma

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      Authors: Charles H. Adelmann; Inbal Rachmin, David E. Fisher
      Abstract: In a new article in the Journal of Investigative Dermatology, Wang et al. (2021) report that mitochondrial quality control modulates responses to endoplasmic reticulum (ER) stress in melanoma. They implicate a linear pathway of XBP1, MARCH5, and MFN2 that act together to regulate mitochondrial fission and mitophagy and ultimately mediate melanoma cell sensitivity to ER stress. This work informs therapeutic combinations and biomarker strategies for targeting melanoma organellar homeostasis as well as for life‒death decisions.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-22
      DOI: 10.1016/j.jid.2021.05.003
       
  • CCL2-CCR2 signaling in the skin drives surfactant-induced irritant contact
           dermatitis via IL-1β-mediated neutrophil accumulation

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      Authors: Rintaro Shibuya; Yoshihiro Ishida, Sho Hanakawa, Tatsuki R. Kataoka, Yasuhide Takeuchi, Teruasa Murata, Arisa Akagi, Zachary Chow, Toshiaki Kogame, Satoshi Nakamizo, Saeko Nakajima, Gyohei Egawa, Takashi Nomura, Naotomo Kambe, Akihiko Kitoh, Kenji Kabashima
      Abstract: Surfactant-induced cumulative irritant contact dermatitis (ICD) is a common and clinically important skin disorder. CCL2 is known to mediate inflammation following tissue damage in various organs. Thus, we investigated whether and how CCL2 contributes to the development of murine cumulative ICD induced by a common surfactant, sodium dodecyl sulfate (SDS). Wild-type mice treated topically with SDS for 6 consecutive days developed skin inflammation that recapitulated the features of human cumulative ICD, including barrier disruption, epidermal thickening, and neutrophil accumulation.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-21
      DOI: 10.1016/j.jid.2021.07.182
       
  • Regulation of IL-17A–Producing Cells in Skin Inflammatory Disorders

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      Authors: Pushpa Pandiyan; Thomas S. McCormick
      Abstract: This review focuses on the IL-17A family of cytokines produced by T lymphocytes and other immune cells and how they are involved in cutaneous pathogenic responses. It will also discuss cutaneous dysbiosis and FOXP3+ regulatory T cells in the context of inflammatory conditions linked to IL-17 responses in the skin. Specifically, it will review key literature on chronic mucocutaneous candidiasis and psoriasis.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-21
      DOI: 10.1016/j.jid.2021.06.036
       
  • Cutaneous liver X receptor activation prevents the formation of
           imiquimod-induced psoriatic dermatitis

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      Authors: Masayuki Otsuka; Gyohei Egawa, Teruki Dainichi, Toshiaki Okuno, Yoshihiro Ishida, Zachary Chow, Ryota Asahina, Toshiya Miyake, Takashi Nomura, Akihiko Kitoh, Takehiko Yokomizo, Kenji Kabashima
      Abstract: Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation (Nestle et al. 2009). In recent years, psoriasis is recognized as an immunometabolic disease associate with multiorgan abnormalities and dyslipidemia (Sterry et al. 2007); however, it remains unclear whether the dysregulation of lipid metabolism in the skin affects the pathogenesis of psoriasis. Liver X receptor (LXR) is a nuclear receptor composed of two isoforms, LXRα (Nr1h3) and LXRβ (Nr1h2) (Chawla et al.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-20
      DOI: 10.1016/j.jid.2021.08.432
       
  • Targeting the human βc receptor inhibits contact dermatitis in a
           transgenic mouse model

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      Authors: Kwok Ho Yip; Duncan McKenzie, Hayley S. Ramshaw, Jessica Chao, Barbara J. McClure, Elmar Raquet, Timo Kraushaar, Joachim Röder, Mhairi Maxwell, Monther Alhamdoosh, Andrew Hammet, Jia Hong Fong, Kathleen Zeglinski, Katherine Monaghan, Harshita Pant, Michele A. Grimbaldeston, Gino Vairo, Nicholas J. Wilson, Catherine M. Owczarek, Timothy R. Hercus, Angel F. Lopez, Damon J. Tumes
      Abstract: Allergic contact dermatitis (ACD) is a prevalent and poorly controlled inflammatory disease caused by skin infiltration of T cells and granulocytes. The βc cytokines GM-CSF, IL-3 and IL-5 are powerful regulators of granulocyte function that signal through their common receptor subunit βc, a property that has made βc an attractive target to simultaneously inhibit these cytokines. However, the species specificity of βc has precluded testing of inhibitors of human βc in mouse models. To overcome this problem, we developed a human βc receptor transgenic (hβcTg) mouse strain with hematopoietic cell-specific expression of human βc instead of mouse βc.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-16
      DOI: 10.1016/j.jid.2021.07.183
       
  • CD39+ Fibroblasts Enhance Myofibroblast Activation by Promoting IL-11
           Secretion in Hypertrophic Scars

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      Authors: Xin Huang; Shuchen Gu, Caiyue Liu, Liang Zhang, Zewei Zhang, Yixuan Zhao, Yimin Khoong, Haizhou Li, Yashan Gao, Yunhan Liu, Zi Wang, Danyang Zhao, Qingfeng Li, Tao Zan
      Abstract: Fibroblasts (Fbs) are critical to hypertrophic scar (HTS) formation and were recently demonstrated to be highly heterogeneous. However, Fb heterogeneity in HTSs has not been fully elucidated. Here, we observed an increased fraction of CD39+ Fbs in HTS after screening four Fb subtypes (CD26+, CD36+, FAP+, and CD39+). CD39+ Fbs, enriched in the upper dermis, were positively correlated with scar severity. The transcriptional analysis of CD39+ and CD39- Fbs sorted from HTS revealed that IL-11 was more highly expressed in CD39+ Fbs.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-16
      DOI: 10.1016/j.jid.2021.07.181
       
  • Cytosolic-DNA-mediated STING-dependent inflammation contributes to the
           progression of psoriasis

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      Authors: Yongsheng Yu; Xiaochun Xue, Wendong Tang, Li Su, Lei Zhang, Yuefan Zhang
      Abstract: Psoriasis is a chronic inflammatory skin disease characterized by an active dynamic interplay between immune cells and keratinocytes. Stimulator of IFN genes (STING) is a universal receptor that recognizes cytosolic DNA and triggers innate immune activation. The aim of current work was to elucidate the role of STING in the inflammation during psoriasis. STING deficiency alleviated psoriatic symptoms and inflammation in mouse models of psoriasis. Stimulation of macrophages with double-stranded DNA (dsDNA) induced STING-dependent release of TNF-α and H2O2 in vitro.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-16
      DOI: 10.1016/j.jid.2021.08.430
       
  • T-Cell‒Mediated Autoimmunity: Mechanisms and Future Directions

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      Authors: Peter Seiringer; Natalie Garzorz-Stark, Kilian Eyerich
      Abstract: T cells are key drivers of autoimmunity in numerous noncommunicable inflammatory skin diseases by directly harming host tissue or through helping B cells in producing autoantibodies. Technological advances have contributed to identifying autoantigens, the Holy Grail of autoimmunity, in many inflammatory disorders of the skin. Novel therapeutic approaches such as chimeric (auto)antibody receptor T cells are a milestone on the way to finding individualized, well-tolerated, targeted therapies. This review summarizes the current knowledge on pathogenesis, immune response pattern‒related ontology, diagnostic approaches, and treatment options of autoimmune skin diseases.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-16
      DOI: 10.1016/j.jid.2021.04.032
       
  • Genome-wide association study identifies three susceptibility loci for
           trichilemmal cysts

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      Authors: Ahmed Yousaf; Michael S. Kolodney
      Abstract: Trichilemmal cysts (TC), also known as pilar cysts, are keratin-filled, subepidermal nodules originating from the outer root sheath of the hair follicle (Leppard et al., 1977). TCs occur sporadically or in an autosomal dominant fashion (Seidenari et al., 2013). Recently, a monoallelic two-hit model affecting PLCD1 was proposed to explain the inheritance of hereditary trichilemmal cysts (Hörer et al., 2019) (Kolodney et al., 2020). A germline variant in PLCD1 (c.1379G>A, p.Ser460Leu) was identified as the major risk allele for familial TCs.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-16
      DOI: 10.1016/j.jid.2021.06.039
       
  • Molecular and cellular characterization of pyoderma gangrenosum:
           Implications for the use of gene expression

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      Authors: Alex G. Ortega-Loayza; Marcia A. Friedman, Ashley M. Reese, Yuangang Liu, Teri M. Greiling, Pamela B. Cassidy, Angelo V. Marzano, Lina Gao, Suzanne S. Fei, James T. Rosenbaum
      Abstract: Pyoderma gangrenosum (PG) is characterized by painful ulcers typically affecting the lower extremities. PG pathogenesis and triggers are poorly understood (Ortega- Loayza AG et al., 2018). Treatments target systemic inflammation, but clinical response and outcomes remain unpredictable. Further investigations are necessary to understand PG pathobiology; however, little is known about gene expression in PG, including whether important changes localize to the dermis or epidermis and whether non-lesional skin from PG patients shows subclinical signs of disease.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-15
      DOI: 10.1016/j.jid.2021.08.431
       
  • Tofacitinib suppresses IL-10/IL-10R signaling and modulates host defense
           responses in human macrophages

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      Authors: Kristin Knoke; Robert R. Rongisch, Katarzyna M. Grzes, Roman Schwarz, Beate Lorenz, Nir Yogev, Erika L. Pearce, Edward J. Pearce, David M. Kofler, Mario Fabri
      Abstract: JAK inhibitors are increasingly used in dermatology. Despite broad inhibitory effects on cytokine signaling cascades, they only modestly increase the risk for infectious diseases. To address molecular mechanisms underlying this unexpected clinical observation, we investigated how tofacintib, a first-in-class JAK inhibitor, regulates host defense responses in TLR4-activated human macrophages. Specifically, we asked if tofacitinib inhibits anti-inflammatory IL-10 signaling, thereby counteracting downregulation of inflammatory, host-protective pathways.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-15
      DOI: 10.1016/j.jid.2021.07.180
       
  • Single-cell analysis reveals MHCII expressing keratinocytes in pressure
           ulcers with worse healing outcomes

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      Authors: Dongqing Li; Shangli Cheng, Yu Pei, Pehr Sommar, Jaanika Kärner, Eva K. Herter, Maria A. Toma, Letian Zhang, Kim Pham, Yuen Ting Cheung, Zhuang Liu, Xingqi Chen, Liv Eidsmo, Qiaolin Deng, Ning Xu Landén
      Abstract: Pressure ulcer (PU) is a chronic wound often seen in spinal cord injury patients and other bed-bound individuals, particularly in the elderly population. Despite its association with high mortality, the pathophysiology of PU remains poorly understood. Here, we compared single-cell transcriptomic profiles of human epidermal cells from PU wound edges with those from uninjured skin and acute wounds (AWs) in healthy donors. We identified significant shifts in the cell composition and gene expression patterns in PU.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-15
      DOI: 10.1016/j.jid.2021.07.176
       
  • Positive Allosteric Modulation of Adenosine A2A Receptor Alters Immune
           Cell Responses and Ameliorates Psoriasis-Like Dermatitis in Mice

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      Authors: Ajith Welihinda; Puja Ravikumar, Manmeet Kaur, Jordan Mechanic, Shruti Yadav, Gyeong Jin Kang, Edward Amento
      Abstract: Psoriasis is an immune cell-mediated inflammatory disease of the skin with a mixed Th1/Th17 cytokine environment combined with an innate immune response engaging toll-like receptors (TLRs). Inflammatory diseases are characterized by dysregulated immune cell responses and elevated levels of adenosine at disease sites. Adenosine, acting through the A2AR, regulates inflammation, immune response, T cell homeostasis and tissue repair. We have identified a unique means to enhance A2AR function using a positive allosteric modulator (PAM).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-15
      DOI: 10.1016/j.jid.2021.07.174
       
  • Loss of AIRE-Mediated Immune Tolerance and the Skin

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      Authors: Pärt Peterson; Kai Kisand, Nicolas Kluger, Annamari Ranki
      Abstract: The core function of the immune response is to distinguish between self and foreign. The multiorgan human autoimmune disease, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED/autoimmune polyendocrine syndrome type 1) is an example of what happens in the body when central immune tolerance goes astray. APECED revealed the existence and function of the autoimmune regulator gene, which has a central role in the development of tolerance. The discovery of autoimmune regulator was the start of a new period in immunology and in understanding the role of central and peripheral tolerance, also very relevant to many skin diseases as we highlight in this review.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-15
      DOI: 10.1016/j.jid.2021.04.022
       
  • Itch in Lichen simplex chronicus is associated with localized small fibre
           neuropathy.

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      Authors: Mauricio Sandoval; Julio Parra, Mauricio Reyna-Jeldes, Maximiliano Curi-Tuma, Fernanda Espinoza, Daniela Muñoz, María Jesús Rojas-Lechuga, Claudio Coddou, David LH. Bennett, Margarita Calvo
      Abstract: Lichen simplex chronicus (LSC), is a common pruritic condition of unknown pathophysiology. The sensory innervation of skin consists of a dermal plexus formed by myelinated and unmyelinated fibres. The epidermis only contains unmyelinated fibres, which signal temperature, pain and/or itch (Ikoma et al. 2006). Intraepidermal fibres can be visualized using the marker PGP 9.5, an ubiquitin C-terminal hydrolase, which is abundantly present in the nervous system (Lauria et al. 2010). Studies of conditions associated with chronic itch have reported increased or decreased intraepidermal nerve fibre density (prurigo nodularis (Johansson et al.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-14
      DOI: 10.1016/j.jid.2021.08.429
       
  • Transcriptomic Repositioning Analysis Identifies mTOR Inhibitor as
           Potential Therapy for Epidermolysis Bullosa Simplex

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      Authors: Gun Ho Lee; Ramrada Lekwuttikarn, Elidia Tafoya, Monica Martin, Kavita Y. Sarin, Joyce M. Teng
      Abstract: Expression-based systematic drug repositioning has been explored to predict novel treatments for a number of skin disorders. Here, we utilize this approach to identify, to our knowledge, previously unreported therapies for epidermolysis bullosa simplex (EBS). RNA sequencing analysis was performed on skin biopsies of acute blisters (
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-14
      DOI: 10.1016/j.jid.2021.07.170
       
  • ONCOSTATIN M IMPROVES CUTANEOUS WOUND RE-EPITHELIALIZATION AND IS
           DEFICIENT UNDER DIABETIC CONDITIONS

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      Authors: Amitava Das; Amit K. Madeshiya, Nirupam Biswas, Nandini Ghosh, Mahadeo Gorain, Atul Rawat, Sanskruti P. Mahajan, Savita Khanna, Chandan K. Sen, Sashwati Roy
      Abstract: Impaired re-epithelialization characterized by hyperkeratotic non-migratory wound epithelium is a hallmark of non-healing diabetic wounds. In chronic wounds, copious release of oncostatin M (OSM) from wound macrophages is evident. OSM is a potent keratinocyte activator. This work sought to understand the signal transduction pathway responsible for wound-re-epithelialization, the primary mechanism underlying wound closure. Daily topical treatment of full-thickness excisional wounds of C57bl/6 mice with recombinant murine OSM improved wound re-epithelialization and accelerated wound closure by bolstering keratinocyte proliferation and migration.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-14
      DOI: 10.1016/j.jid.2021.04.039
       
  • Combined CDK inhibition overcomes MEK inhibitor resistance in plexiform
           neurofibroma of neurofibromatosis type I

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      Authors: Wei Wang; Xi-Wei Cui, Yi-Hui Gu, Cheng-Jiang Wei, Yue-Hua Li, Jie-Yi Ren, Man-hon Chung, Re-han-gu-li Aimaier, Hai-Bing Zhang, Qing-Feng Li, Zhi-Chao Wang
      Abstract: MEK1/2 inhibitors (MEKi) have recently achieved surprising success in treating unresectable plexiform neurofibromas (PNFs). However, few studies have investigated the mechanisms of MEKi resistance in PNF patients. We determined the efficacy of 6 different MEKi for treating PNFs, explored drug resistance mechanisms and identified potential combination therapies to overcome resistance. By screening drug efficacy among 6 MEKi in human NF1-deficient PNF cell lines, TAK-733 was found reduce PNF cell viability the most.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-14
      DOI: 10.1016/j.jid.2021.07.164
       
  • IL-10 Dysregulation Underlies Chemokine Insufficiency, Delayed Macrophage
           Response, and Impaired Healing in Diabetic Wound

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      Authors: Ruchi Roy; Janet Zayas, Mohamed F. Mohamed, Anahita Aboonabi, Kaylee Delgado, Jennillee Wallace, Mohammad Bayat, Timothy M. Kuzel, Jochen Reiser, Sasha H. Shafikhani
      Abstract: Persistent inflammation is a major contributor to healing impairment in diabetic chronic wounds. Paradoxically, diabetic wound environment during the acute phase of healing is completely different in that it exhibits reduced macrophage response due to inadequate expression of CCL2 proinflammatory cytokine. What causes reduction in CCL2 expression in diabetic wound early after injury remains unknown. Here, we report that in contrast to prolonged exposure to high glucose which transforms monocytes proinflammatory, short-term exposure to high glucose causes a rapid monocyte reprograming, manifested by increased expression and secretion of IL-10 which in an autocrine/paracrine fashion, reduces glucose uptake and transforms monocytes into anti-inflammatory phenotype by dampening signaling through toll-like receptors (TLRs).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-10
      DOI: 10.1016/j.jid.2021.08.428
       
  • Activin A sustains the metastatic phenotype of tumor associated
           macrophages and is a prognostic marker in human cutaneous melanoma

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      Authors: Alba Gutiérrez-Seijo; Elena García-Martínez, Celia Barrio-Alonso, Verónica Parra-Blanco, José Antonio Avilés-Izquierdo, Paloma Sánchez-Mateos, Rafael Samaniego
      Abstract: Tumor cells attract and dynamically interact with monocytes/macrophages to subvert their differentiation into tumor associated macrophages (TAMs), which mainly promote immune suppression and neoplastic progression, but the pathways and microenvironmental cues governing their protumoral deviation are not completely understood. To identify molecular pathways responsible for TAM differentiation we screened biomarkers secreted during melanoma-macrophage interactions using Quantibody® microarrays and RNAseq of macrophages.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-06
      DOI: 10.1016/j.jid.2021.07.179
       
  • Specific β-defensins stimulate pruritus through activation of sensory
           neurons

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      Authors: Pang-Yen Tseng; Mark A. Hoon
      Abstract: Pruritus is a common symptom of dermatological disorders and has a major negative impact of quality of life. Previously, it was suggested that skin derived β-defensin peptides elicit itch through activation of mast cells. Here we investigated, in more detail, the mechanisms by which β-defensins induce itch by defining the receptors activated by these peptides in humans and mice, by establishing their action in vivo, and examining their expression in dermal diseases. We found in psoriasis and atopic dermatitis, elevated expression of DEFB103 is highly correlated with skin lesions.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-01
      DOI: 10.1016/j.jid.2021.07.178
       
  • Genomic progression of precancerous actinic keratosis to squamous cell
           carcinoma

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      Authors: Yoon-Seob Kim; Sun Shin, Seung-Hyun Jung, Young Min Park, Gyeong Sin Park, Sug Hyung Lee, Yeun-Jun Chung
      Abstract: The mechanism underlying the progression of actinic keratosis (AK) and cutaneous squamous cell carcinoma in situ (SCCIS) to squamous cell carcinoma (SCC) remains unclear. To investigate this, we performed regional microdissection and targeted deep sequencing in SCC (N=10) and paired adjacent SE (sun-damaged epidermis)/AK/SCCIS (N=13) samples to detect mutations and copy number alterations (CNAs). Most (11/13) SE/AK/SCCIS tissues harbored ≥ 1 driver alterations, indicating their precancerous nature.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-09-01
      DOI: 10.1016/j.jid.2021.07.172
       
  • Merkel cell polyomavirus-negative -Merkel cell carcinoma originating from
           in situ squamous cell carcinoma: a keratinocytic tumor with neuroendocrine
           differentiation

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      Authors: Thibault Kervarrec; Silke Appenzeller, Mahtab Samimi, Bhavishya Sarma, Eva-Maria Sarosi, Patricia Berthon, Yannick Le Corre, Ewa Hainaut-Wierzbicka, Astrid Blom, Nathalie Benethon, Guido Bens, Charline Nardin, Francois Aubin, Monica Dinulescu, Marie-Laure Jullie, Ágnes Pekár-Lukacs, Eduardo Calonje, Soumanth Thanguturi, Anne Tallet, Marion Wobser, Antoine Touzé, Serge Guyétant, Roland Houben, David Schrama
      Abstract: While virus-negative Merkel cell carcinoma (MCC) is characterized by high frequency of UV-induced mutations, expression of two viral oncoproteins is regarded as key mechanism driving Merkel cell polyomavirus (MCPyV)-positive MCC. The cells in which these molecular events initiate MCC oncogenesis have yet not been identified for both MCC subsets. A considerable proportion of virus-negative MCC is found in association with squamous cell carcinoma (SCC) suggesting (i) coincidental collision, (ii) one providing a niche for the other or (iii) one evolving from the other.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-31
      DOI: 10.1016/j.jid.2021.07.175
       
  • Immunocompromised patients with therapy-refractory chronic skin diseases
           show reactivation of latent EBV and CMV infection

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      Authors: Philipp Speth; Manja Jargosch, Peter Seiringer, Kristina Schwamborn, Tanja Bauer, Cora Scheerer, Ulrike Protzer, Carsten Schmidt-Weber, Tilo Biedermann, Stefanie Eyerich, Natalie Garzorz-Stark
      Abstract: Reactivation of latent Epstein-Barr virus (EBV) and/or Cytomegalovirus (CMV) infection is a dreaded complication in immunocompromised patients receiving hematopoietic stem cell transplantation. Evidence is sparse if subclinical reactivation of viral infection may also be of clinical relevance in dermatological patients. We screened patients (n= 206) suffering from chronic skin diseases for subclinical reactivation of EBV and CMV infection. We found that immunocompromised patients with therapy-refractory chronic skin diseases showed higher rates of subclinical reactivation of CMV and EBV infection (6.7 % vs.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-31
      DOI: 10.1016/j.jid.2021.07.171
       
  • The Skin's Barrier: A Cryo-EM Based Overview of its Architecture and
           Stepwise Formation

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      Authors: Lars Norlén; Magnus Lundborg, Christian Wennberg, Ali Narangifard, Bertil Daneholt
      Abstract: A major role of the skin is to serve as a barrier toward the environment. The skin's permeability barrier consists of a lipid structure positioned in the stratum corneum. Recent progress in high-resolution cryo-electron microscopy (cryo-EM) has allowed for elucidation of the architecture of the skin's barrier and its stepwise formation process representing the final stage of epidermal differentiation. In this review, we present an overview of the skin's barrier structure and its formation process, as evidenced by cryo-EM.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-31
      DOI: 10.1016/j.jid.2021.06.037
       
  • Viral Status Predicts Patterns of Genome Methylation and Decitabine
           Response in Merkel Cell Carcinoma

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      Authors: Paul W. Harms; Monique E. Verhaegen, Josh N. Vo, Jean C. Tien, Drew Pratt, Fengyun Su, Saravana M. Dhanasekaran, Xuhong Cao, Doris Mangelberger, Julia VanGoor, Jae Eun Choi, Vincent T. Ma, Andrzej A. Dlugosz, Arul M. Chinnaiyan
      Abstract: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that is classified as Merkel cell polyomavirus (MCPyV)-positive or virus-negative. Epigenetic changes, such as DNA methylation, can alter gene expression and influence cancer progression. However, patterns of DNA methylation and the therapeutic efficacy of hypomethylating agents have not been fully explored in MCC. We characterized genome-wide DNA methylation in 16 MCC cell lines from both molecular subclasses in comparison to other cancer types, and found that the overall profile of MCC is similar to small cell lung carcinoma.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-29
      DOI: 10.1016/j.jid.2021.07.173
       
  • The Temporal Evolution of Distinct Skin Surface Microbiome in Asian Severe
           Hidradenitis Suppurativa Patients during Effective Adalimumab Treatment

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      Authors: Ting-Jung Hsu; Hsu-Hang Yeh, Chih-Hung Lee, Han-Chi Tseng
      Abstract: Hidradenitis suppurativa (HS) is a debilitating, chronic recurrent inflammatory disease primarily involving the folliculopilosebaceous units of the intertriginous areas. Abscesses, sinus tracts, fistulas, and scarring may occur in severe cases and negatively impact the quality of life of the patients(Hunger et al., 2017, Saunte and Jemec, 2017). Bacteria have been implicated in the pathogenesis of the disease, but their role remains unclear(Nikolakis et al., 2017).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-27
      DOI: 10.1016/j.jid.2021.07.168
       
  • Epidermis-intrinsic transcription factor Ovol1 coordinately regulates
           barrier maintenance and neutrophil accumulation in psoriasis-like
           inflammation

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      Authors: Morgan Dragan; Peng Sun, Zeyu Chen, Xianghui Ma, Remy Vu, Yuling Shi, S. Armando Villalta, Xing Dai
      Abstract: Skin epidermis constitutes the exterior barrier that protects the body from dehydration and environmental assaults. Barrier defects underlie common inflammatory skin diseases, but the molecular mechanisms that maintain barrier integrity and regulate epidermal-immune cell cross-talk in inflamed skin are not fully understood. Here we show that skin epithelia-specific deletion of Ovol1 (ovo-like 1), which encodes a skin disease-linked transcriptional repressor, impairs the epidermal barrier and aggravates psoriasis-like skin inflammation in mice in part through enhancing neutrophil accumulation and abscess formation.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-27
      DOI: 10.1016/j.jid.2021.08.397
       
  • Role of Exosomes in Dermal Wound Healing: A Systematic Review

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      Authors: Anesh Prasai; Jayson W. Jay, Daniel Jupiter, Steven E. Wolf, Amina El Ayadi
      Abstract: Cell-based therapy imparts its therapeutic effects via soluble growth factors and vesicular bodies like exosomes. A systematic review with a meta-analysis of pre-clinical studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the modified Stroke Therapy Academic Industry Roundtable (STAIR) guidelines, to identify exosomes as an archetype biological therapy for dermal wound healing and to provide guidelines for the concentrations to be used in pre-clinical studies.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-27
      DOI: 10.1016/j.jid.2021.07.167
       
  • Core gene signatures of atopic dermatitis using public RNA-sequencing
           resources: Comparison of bulk vs. single-cell approach

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      Authors: Kyung Bae Chung; Jongwook Oh, Won Seok Roh, Tae-Gyun Kim, Do-Young Kim
      Abstract: Next-generation sequencing, particularly RNA sequencing, has revolutionized dermatological research as a powerful tool to discover core pathologies. The primary RNA sequencing approaches are bulk-tissue RNA sequencing (bulk-seq) and single-cell RNA sequencing (scRNA-seq). Bulk-seq measures average gene expression of heterogeneous cell populations, and scRNA-seq identifies heterogeneity at a single-cell resolution. Although scRNA-seq can identify cell populations not identified by bulk-seq, inherent limitations present challenges.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-26
      DOI: 10.1016/j.jid.2021.07.169
       
  • Interaction of galectin-7 with HMGCS1 in vitro may facilitate cholesterol
           deposition in cultured keratinocytes

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      Authors: Norihiro Fujimoto; Minoru Akiyama, Yasushi Satoh, Shingo Tajima
      Abstract: Three-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase 1 (HMGCS1) was identified to interact with Gal-7, a pro-apoptotic β-galactoside binding protein, by yeast two-hybrid system. Their interaction was confirmed by in vitro β-galactosidase, BIA core and immunoprecipitation assays. Distinct interactive site of HMGCS1was found to reside at Phe-26. The expression of HMGCS1 in cultured keratinocytes was up-regulated by exogenous Gal-7 and down-regulated in Gal-7 siRNA transfected cells. HMGCS1-overexpressing cells were found to induce Gal-7 expression, which suggests that Gal-7 and HMGCS1 expressions are both stimulated by a positive feedback regulation.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-26
      DOI: 10.1016/j.jid.2021.04.038
       
  • B lymphocytes accumulate and proliferate in human skin at sites of
           cutaneous antigen challenge

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      Authors: Isioma U. Egbuniwe; Robert J. Harris, Mano Nakamura, Frank O. Nestle, Arne N. Akbar, Sophia N. Karagiannis, Katie E. Lacy
      Abstract: To the Editor, B cells play important roles in skin diseases (Egbuniwe et al., 2015) and in cutaneous homeostasis (Geherin et al., 2012, Geherin et al., 2016, Nihal et al., 2000). Mature class-switched IgG+ B cells have been detected in normal human skin (Saul et al., 2016) featuring clonally-restricted B cell receptors, indicating narrow antigenic repertoires (Nihal et al., 2000). However, the involvement of B cells during an antigenic stimulus in human skin remains unexplored. B cells are relatively scarce in normal human skin (Supplementary Figure 1), explaining why past studies have primarily focused on T cells which constitute the major skin-resident lymphocyte population (Clark et al., 2006b, Jiang et al., 2012, Sanchez Rodriguez et al., 2014).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-24
      DOI: 10.1016/j.jid.2021.06.038
       
  • Co-expression of MTH1 and PMS2 is associated with advanced disease and
           disease progression after therapy in melanoma

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      Authors: Ishani Das; Rainer Tuominen, Thomas Helleday, Johan Hansson, Ulrika Warpman Berglund, Suzanne Egyházi Brage
      Abstract: To the Editor
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-18
      DOI: 10.1016/j.jid.2021.07.166
       
  • Photosensitivity and cGAS-dependent type I IFN activation in lupus
           patients with TREX1 deficiency

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      Authors: Nicole Berndt; Christine Wolf, Kristina Fischer, Emanuel Cura Costa, Peter Knuschke, Nick Zimmermann, Franziska Schmidt, Martin Merkel, Osvaldo Chara, Min Ae Lee-Kirsch, Claudia Günther
      Abstract: The exonuclease three prime repair exonuclease 1 (TREX1) safeguards the cell against DNA accumulation in the cytosol and thereby prevents innate immune activation and autoimmunity. TREX1 mutations lead to chronic DNA damage and cell-intrinsic type I interferon (IFN) response. Associated disease phenotypes include Aicardi-Goutières syndrome, familial chilblain lupus and systemic lupus erythematosus. Given the role of ultraviolet (UV) light in lupus pathogenesis, we assessed sensitivity to UV light in lupus patients with TREX1 mutation by phototesting which revealed an enhanced photosensitivity.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-13
      DOI: 10.1016/j.jid.2021.04.037
       
  • Altered Skin and Gut Microbiome in Hidradenitis Suppurativa

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      Authors: S. McCarthy; M. Barrett, S. Kirthi, P. Pellanda, K. Vlckova, A.M. Tobin, M. Murphy, F. Shanahan, P.W. O’Toole
      Abstract: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by the formation of nodules, abscesses, and fistula at intertriginous sites. The skin-gut axis is an area of emerging research in inflammatory skin disease and is a potential contributory factor to the pathogenesis of HS. 59 patients with HS provided fecal samples, nasal and skin swabs of affected sites for analysis. 30 healthy controls provided fecal samples and 20 healthy controls provided nasal and skin swabs. We performed bacterial 16S rRNA gene amplicon sequencing on total DNA derived from the samples.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-05
      DOI: 10.1016/j.jid.2021.05.036
       
  • Interferon Kappa Is a Rheostat for Development of Psoriasiform
           Inflammation

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      Authors: Mehrnaz Gharaee-Kermani; Shannon N. Estadt, Lam C. Tsoi, Sonya J. Wolf, Jianhua Liu, Xianying Xing, Jonathon Theros, Tammi J. Reed, Lori Lowe, Dennis Gruszka, Nicole L. Ward, Johann E. Gudjonsson, J. Michelle Kahlenberg
      Abstract: Psoriasis is a common, inflammatory autoimmune skin disease. Early detection of a type I interferon (IFN) signature occurs in many psoriasis lesions, but the source of IFN production remains debated. Interferon kappa (IFN-κ) is an important source of type I IFN production in the epidermis. We identified a correlation between IFN–regulated and psoriasis-associated genes in human lesional skin. We thus wanted to explore the effects of IFN-κ in psoriasis using the well-characterized imiquimod (IMQ) psoriasis model.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-05
      DOI: 10.1016/j.jid.2021.05.029
       
  • Understanding and Harnessing Epithelial‒Mesenchymal Interactions in the
           Development of Palmoplantar Identity

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      Authors: Jerry Tsai; Mary Rostom, Luis A. Garza
      Abstract: Palmoplantar skin has several unique characteristics such as increased thickness, high resilience, hypopigmentation, and lack of hair follicles. The establishment of palmoplantar identity occurs through keratinocyte‒fibroblast interactions, with keratin 9 expression and Wnt signaling playing key roles. Understanding how palmoplantar features develop may help efforts to reproduce them at both palmoplantar and nonpalmoplantar body sites.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-05
      DOI: 10.1016/j.jid.2021.06.016
       
  • Assessing the risk and outcome of COVID-19 in patients with psoriasis or
           psoriatic arthritis on biologic treatment: a critical appraisal of the
           quality of the published evidence

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      Authors: Stefano Piaserico; Paolo Gisondi, Simone Cazzaniga, Sara Di Leo, Luigi Naldi
      Abstract: The need to rapidly spread information about the risk of COVID-19 in patients with psoriasis (Pso) and psoriatic arthritis (PsA) on biologics may have hampered the methodological rigor in published literature. We analysed the quality of papers dealing with the risk and outcomes of COVID-19 in patients with Pso and PsA receiving biologic therapies. The Newcastle-Ottawa Scale (NOS) was used to estimate the quality of the published studies. Moreover, to better contextualize results, specific internal and external validity items were further considered, i.e.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-04
      DOI: 10.1016/j.jid.2021.04.036
       
  • MC1R Functions, Expression, and Implications for Targeted Therapy

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      Authors: Stefania Guida; Gabriella Guida, Colin Ronald Goding
      Abstract: The G protein-coupled MC1R is expressed in melanocytes and has a pivotal role in human skin pigmentation, with reduced function in human genetic variants exhibiting a red hair phenotype and increased melanoma predisposition. Beyond its role in pigmentation, MC1R is increasingly recognized as promoting UV-induced DNA damage repair. Consequently, there is mounting interest in targeting MC1R for therapeutic benefit. However, whether MC1R expression is restricted to melanocytes or is more widely expressed remains a matter of debate.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-04
      DOI: 10.1016/j.jid.2021.06.018
       
  • LPCAT1 promotes cutaneous squamous cell carcinoma via EGFR-mediated
           AKT/p38MAPK signaling pathways

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      Authors: Yingjian Huang; Yuqian Wang, Yan Wang, Ning Wang, Qiqi Duan, Shengbang Wang, Meng Liu, Muhammad Ahsan Bilal, Yan Zheng
      Abstract: Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer. LPCAT1, a lysophosphatidylcholine acyltransferase, takes a center stage in the membrane lipid remodeling. LPCAT1 is elevated in several cancers and contributes to cancer development. However, its role and molecular mechanisms in cSCC remain to be elucidated. In the present study, we found that LPCAT1 was up-regulated in cSCC tissues and cell lines. In vitro, loss-of-function and gain-of-function experiments demonstrated that LPCAT1 facilitated cSCC cell proliferation, protected cells against apoptosis, accelerated epithelial-mesenchymal transition (EMT), and enhanced cell metastasis.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-03
      DOI: 10.1016/j.jid.2021.07.163
       
  • The evolution of acquired resistance to BRAF inhibitor is sustained by
           IGF1-driven tumor vascular remodeling

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      Authors: Guangchao Xu; Ya Luo, Wenshuang Wu, Xiaowei Liu, Xin Yu, Yu Bao, Xiujing He, Jing Yu, Yanna Li, Jiqiao Yang, Rongjie Zhang, Chune Yu, Hongying Chen, Jie Xu, Jianping Hu, Jing Jing, Hubing Shi
      Abstract: As hallmark of cancer, angiogenesis plays a pivotal role in carcinogenesis. The correlation between angiogenesis and evolution of BRAF inhibitor acquired resistance is, however, still poorly understood. Here, we reported that the molecular signatures of angiogenesis were enriched in early on-treated biopsies but not in disease progressed biopsies. The process of drug resistance development was accompanied by remodeling of vascular morphology, which was potentially manipulated by tumor-secreted pro-angiogenic factors.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-03
      DOI: 10.1016/j.jid.2021.07.162
       
  • Epigenetic regulation of apoptosis in cutaneous T-cell lymphoma (CTCL):
           implications for therapy with methotrexate, JAK inhibitors and resveratrol
           

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      Authors: Minakshi Nihal; Jinqiang Wu, Connor J. Stonesifer, Jay Daniels, Jaehyuk Choi, Larisa Geskin, Alain H. Rook, Gary S. Wood
      Abstract: Previously, we showed that deficiencies in apoptotic factors occur in CTCL and can be enhanced through epigenetic mechanisms (Stutz et al., 2012; Wu et al., 2009; Wu and Wood, 2011). Now we have further explored the epigenetic regulation of apoptosis in CTCL with special attention to the DNMT/STAT3 promoter methylation complex responsible for silencing several tumor suppressor genes including those involved in apoptosis. We report that the combination of DNA methylation inhibitor (methotrexate, MTX), JAK inhibitor (fedratinib, FED) and lysine acetylase inhibitor (resveratrol, RES) can induce robust cell death in CTCL lines and leukemic Sezary cells.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-03
      DOI: 10.1016/j.jid.2021.06.034
       
  • Sex Bias and Autoimmune Diseases

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      Authors: Enze Xing; Allison C. Billi, Johann E. Gudjonsson
      Abstract: Sex bias in immune function has been well-described, and women have been shown to counter immunologically stimulating phenomena such as infection, malignancy, and trauma with more protective responses than men. Heightened immunity in women may also result in a predisposition for loss of self-tolerance and development of autoimmunity, reflected by the overwhelming female sex bias of patients with autoimmune diseases. In this review, we discuss the postulated evolutionary etiologies for sexual dimorphism in immunity.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-03
      DOI: 10.1016/j.jid.2021.06.008
       
  • Naturally occurring Telomerase-specific CD4 T cell Immunity in Melanoma

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      Authors: Charlée Nardin; Caroline Laheurte, Eve Puzenat, Laura Boullerot, Mélanie Ramseyer, Amélie Marguier, Marion Jacquin, Yann Godet, François Aubin, Olivier Adotevi
      Abstract: CD4 T cells play a key role in anticancer immunity. Here, we investigate the clinical relevance of circulating CD4 Th1 response against telomerase (anti-TERT Th1 response) in melanoma patients.The spontaneous anti-TERT Th1 response was detected in 54.5% (85/156) of melanoma patients before treatment. The prevalence of this systemic response was inversely related to Breslow thickness above 1mm and AJCC stage ≥ II (P = 0.001 and 0.032). In contrast to patients treated by targeted therapies, the anti-TERT Th1 immunity was associated with objective response after immune checkpoint inhibitors (ICI) treatment.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-02
      DOI: 10.1016/j.jid.2021.07.160
       
  • Deciphering the role of skin surface microbiome in skin health: an
           integrative multi-omics approach reveals three distinct metabolite-microbe
           clusters

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      Authors: Pierre-François Roux; Thierry Oddos, Georgios Stamatas
      Abstract: The advent of 16S RNA profiling and shotgun metagenomics has enabled a holistic approach to the study of the skin microbiome composition. Despite the interesting findings in this rapidly developing scientific area, the big question remains: What role does the microbiome play in skin physiology' To begin answering this question, we employed an integrative methodology for microbiome and metabolome analysis of skin surface samples collected from the volar forearm of healthy 3 to 6-month-old infants.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-02
      DOI: 10.1016/j.jid.2021.07.159
       
  • Increased activation of innate immunity and pro-apoptotic CXCR3B in
           ‘normal-appearing’ skin on the lesional side of patients with
           segmental vitiligo

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      Authors: Thierry Passeron; Valentina EA. Malmqvst, Hanene Bzioueche, Sandrine Marchetti, Stephane Rocchi, Meri K. Tulic
      Abstract: To the Editor, The mechanisms involved in pathogenesis of segmental vitiligo (SV) is poorly understood. Due to its characteristic asymmetric unilateral distribution of depigmentation, proposed hypotheses include melanocytes and/or keratinocytes carrying mosaic mutation and being intrinsically abnormal and/or more susceptible to stress. Moreover, a subclinical inflammatory response is now well demonstrated also in segmental forms of vitiligo (Speeckaert et al., 2020) and the involvement of CD8+ melanocyte specific T cell-mediated immunity as is observed in generalized vitiligo (van Geel et al.).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-02
      DOI: 10.1016/j.jid.2021.07.157
       
  • IL-22 downregulates peptidylarginine deiminase-1 in human keratinocytes:
           adding another piece to the IL-22 puzzle in epidermal barrier formation

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      Authors: Avinash Padhi; Ankit Srivastava, Abarajitha Ramesh, Marcus Ehrström, Michel Simon, Enikö Sonkoly, Liv Eidsmo, Peter Bergman, Josefin Lysell
      Abstract: Increased presence of interleukin (IL)-22+ cells in the skin is a characteristic finding in skin barrier defects, such as atopic dermatitis (AD) and psoriasis. However, mechanistic insights into effects of IL-22 on epidermal functioning is yet to be elucidated. One crucial step during epidermal differentiation is deimination or citrullination. Here we show reduced levels of peptidylarginine deiminase 1(PAD1), enzyme that converts peptidyl-arginine into citrulline in lesional psoriatic skin. IL-22 signaling through the IL-22 receptor complex was found to suppress expression of PAD1 in epidermal keratinocytes.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-02
      DOI: 10.1016/j.jid.2021.07.155
       
  • Differential pathomechanisms of desmoglein-1 transmembrane domain
           mutations in skin disease

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      Authors: Stephanie E. Zimmer; Takuya Takeichi, Daniel E. Conway, Akiharu Kubo, Yasushi Suga, Masashi Akiyama, Andrew P. Kowalczyk
      Abstract: Dominant and recessive mutations in the desmosomal cadherin, desmoglein-1 (DSG1), cause the skin diseases palmoplantar keratoderma (PPK) and severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome, respectively. Here, we compare two dominant missense mutations in the DSG1 transmembrane domain (TMD), G557R and G562R, causing PPK (DSG1PPK-TMD) and SAM syndrome (DSG1SAM-TMD), respectively, to determine the differing pathomechanisms of these mutants. Expressing the DSG1TMD mutants in a DSG-null background, we use cellular and biochemical assays to reveal differences in the mechanistic behavior of each mutant.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-02
      DOI: 10.1016/j.jid.2021.07.154
       
  • Barrier Function in Aging: Comments on Pilkington, et al.
           “Inflammaging and the Skin”

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      Authors: Peter M. Elias
      Abstract: To the Editor:
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-02
      DOI: 10.1016/j.jid.2021.07.134
       
  • Differences in Psychometric Properties of Clinician and Patient-reported
           Outcome Measures for Atopic Dermatitis By Race and Skin Tone: A Systematic
           Review

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      Authors: Trisha Kaundinya; Uros Rakita, Armaan Guraya, Donna Maria Abboud, Emily Croce, Jacob P. Thyssen, Andrew Alexis, Jonathan I. Silverberg
      Abstract: Psychometric validity and reliability of widely used atopic dermatitis (AD) outcome measures across different race and ethnicity is unclear. We describe rates of reporting race, ethnicity and skin tone in studies testing psychometric properties of AD outcome measures and compare psychometric analyses across race, ethnicity, and skin tone. We systematically reviewed MEDLINE and EMBASE for studies reporting psychometric properties of clinician reported (ClinROM) or patient reported outcome measures (PROM) in AD (PROSPERO: CRD42021239614).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-02
      DOI: 10.1016/j.jid.2021.06.033
       
  • Measurement properties of patient-reported outcome measures for pruritus:
           An updated systematic review

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      Authors: J. Topp; C. Apfelbacher, S. Ständer, M. Augustin, C. Blome
      Abstract: This systematic review aims to provide an update on measurement properties of patient-reported outcome measures for pruritus. A Medline literature search was conducted to update the systematic review published by Schoch et al. in 2017 and to identify new validation studies published between October 2015 and July 2019. The methodological quality of validation studies was assessed based on the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist and the measurement properties of patient-reported outcome measures were evaluated.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-02
      DOI: 10.1016/j.jid.2021.06.032
       
  • ZFP36 family members regulate the pro-inflammatory features of psoriatic
           dermal fibroblasts

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      Authors: Chiara Angiolilli; Emmerik F.A. Leijten, Cornelis P.J. Bekker, Ella Eeftink, Barbara Giovannone, Michel Olde Nordkamp, Marlot van der Wal, Judith L. Thijs, Sebastiaan J. Vastert, Femke van Wijk, Timothy R.D.J. Radstake, Jorg van Loosdregt
      Abstract: Dermal fibroblasts are strategically positioned underneath the basal epidermis layer to support keratinocyte proliferation and extracellular matrix production. In inflammatory conditions, these fibroblasts produce cytokines and chemokines that promote the chemoattraction of immune cells into the dermis and the hyperplasia of the epidermis, two characteristic hallmarks of Psoriasis (Pso). However, how dermal fibroblasts specifically contribute to Pso development remains largely uncharacterized.Here we investigated through which cytokines and signaling pathways dermal fibroblasts contribute to the inflammatory features of psoriatic skin.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-08-02
      DOI: 10.1016/j.jid.2021.06.030
       
  • Cytokine Stimulation via MRGPRX2 Occurs with Lower Potency than by
           FcεRI-aggregation but with Similar Dependence on the ERK1/2 Module in
           Human Skin Mast Cells

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      Authors: Zhao Wang; Kristin Franke, Torsten Zuberbier, Magda Babina
      Abstract: Skin mast cells (MCs) contribute to chronic dermatoses that partially rely on MC-derived cytokines. The discovery of MRGPRX2 explains MC-dependent symptoms independently of FcεRI-activation. Here, we investigated whether MRGPRX2 can elicit cytokines, determined its relative potency versus FcεRI and addressed the underlying mechanisms. MRGPRX2-activation by compound 48/80 or Substance P on skin MCs induced TNF-α, IL-8, IL-13, CCL1, CCL2 mRNA and protein, yet induction was typically reduced compared with FcεRI-crosslinking.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-27
      DOI: 10.1016/j.jid.2021.07.153
       
  • The Role of CNTNAP2 in Itch Sensation

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      Authors: Santosh K. Mishra
      Abstract: To the Editor
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-23
      DOI: 10.1016/j.jid.2021.07.152
       
  • Lack of significant association between sex hormone concentrations and
           atopic dermatitis in adolescents and adults in two population-based
           studies

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      Authors: Hanna Kische; Anke Hannemann, Catharina Voss, Matthias Nauck, Henry Völzke, Lars Pieper, Katja Beesdo-Baum, Andreas Arnold
      Abstract: Atopic dermatitis (AD) is a chronic, pruritic skin disease with increasing incidence (Mathiesen and Thomsen, 2019). While AD is classically thought of as a paediatric disease, recent studies have shown high rates of disease in adults as well, with a prevalence in Europe between 2.2% and 17.6% (Kowalska-Olędzka et al., 2019). There is a growing body of evidence, that sex hormones play a role in the complex interplay of ADs pathophysiology, influencing immunological pathways and the skin (Kanda et al., 2019).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-23
      DOI: 10.1016/j.jid.2021.07.133
       
  • Transcriptomic Analysis of Blaschko-Linear Psoriasis Reveals Shared and
           Distinct Features with Psoriasis Vulgaris

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      Authors: Alexandros Onoufriadis; Umar Niazi, Konstantina Dimitrakopoulou, Jeremias Reich, Chrysanthi Ainali, Maria Papanikolaou, Evangelia Kesidou, Chao-Kai Hsu, Mansoor Saqi, John A. McGrath, Kristian Reich
      Abstract: To the Editor, Psoriasis is a common chronic inflammatory skin disease characterized by abnormal proliferation/differentiation of keratinocytes and increased immune cell infiltration in the dermis and epidermis (Greb et al., 2016). Although immune cells are considered to be the main driver of psoriasis, keratinocytes may also be implicated in triggering psoriasis and in sustaining inflammation in psoriatic skin (Ni and Lai, 2020). Psoriasis can manifest clinically in several different ways (Boehncke and Schön, 2015), but the rare observation that some individuals may present with psoriasis along the lines of Blaschko (Blaschko, 1901), i.e.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-23
      DOI: 10.1016/j.jid.2021.07.007
       
  • CLEC12B decreases melanoma proliferation by repressing STAT3

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      Authors: Henri Montaudié; Laura Sormani, Bérengère Dadone-Montaudié, Marjorie Heim, Nathalie Cardot-Leccia, Meri K. Tulic, Guillaume Beranger, Anne-Sophie Gay, Delphine Debayle, Yann Cheli, Jérémy H. Raymond, Pierre Sohier, Valérie Petit, Stéphane Rocchi, Franck Gesbert, Lionel Larue, Thierry Passeron
      Abstract: The potential role of CLEC12B, a gene predominantly expressed by skin melanocytes discovered through transcriptomic analysis, in melanoma is unknown. Here we show that CLEC12B expression is lower in melanoma and melanoma metastases than in melanocytes and benign melanocytic lesions, and that its decrease correlates with a poor prognosis. We further show that CLEC12B recruits SHP2 phosphatase through its ITIM domain, inactivates STAT1/3/5, increases p53/p21/p27 expression/activity and modulates melanoma cell proliferation.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-23
      DOI: 10.1016/j.jid.2021.05.035
       
  • Differential involvement of programmed cell death ligands in skin immune
           responses

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      Authors: Ryota Tanaka; Yuki Ichimura, Noriko Kubota, Akimasa Saito, Yoshiyuki Nakamura, Yosuke Ishitsuka, Rei Watanabe, Yasuhiro Fujisawa, Seiya Mizuno, Satoru Takahashi, Manabu Fujimoto, Naoko Okiyama
      Abstract: Programmed cell death-1 (PD-1) is an immuno-regulatory receptor that can bind PD-L1 or PD-L2 expressed on stimulated antigen-presenting cells. In this study, isolated antigen-presenting cells (macrophages and dendritic cells) were cultured with interferon (IFN)-γ, interleukin (IL)-4, or IL-17A and expression of PD-L1 and PD-L2 was compared by flow cytometry. Strong upregulation of PD-L1 expression was observed upon IFN-γ stimulation of both antigen-presenting cells, as well as in response to IL-17A stimulation of macrophages compared to unstimulated controls.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-23
      DOI: 10.1016/j.jid.2021.06.026
       
  • Interferon regulatory factor 6 regulates the delivery of E-cadherin to the
           plasma membrane

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      Authors: Angelo Antiguas; Kris A. DeMali, Martine Dunnwald
      Abstract: Interferon Regulatory Factor 6 (IRF6) is a transcription factor that is required for craniofacial development and epidermal morphogenesis. Specifically, Irf6-deficient mice lack the terminally differentiated epidermal layers, leading to the absence of barrier function. This phenotype also includes intraoral adhesions due to the abscence of the oral periderm, leading to the mislocalization of E-cadherin and other cell-cell adhesion proteins of the oral epithelium. However, the mechanisms by which IRF6 control the localization of cell adhesion proteins is not understood.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-22
      DOI: 10.1016/j.jid.2021.06.031
       
  • Inhibition of CtBP-regulated proinflammatory gene transcription attenuates
           psoriatic skin inflammation

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      Authors: Hong Li; Caiguo Zhang, Li Bian, Hui Deng, Melanie Blevins, Gangwen Han, Bin Fan, Chunxia Yang, Rui Zhao, Whitney High, David Norris, Mayumi Fujita, Xiao-Jing Wang, Mingxia Huang
      Abstract: Psoriasis is a chronic immune-mediated disease characterized by excessive proliferation of epidermal keratinocytes and increased immune cell infiltration to the skin. Although it is well known that psoriasis pathogenesis is driven by aberrant production of proinflammatory cytokines, the mechanisms underlying the imbalance between proinflammatory and anti-inflammatory cytokine expression are incompletely understood. Here we report that the transcriptional coregulators C-terminal-binding protein (CtBP) 1 and 2 can transactivate a common set of proinflammatory genes both in the skin of imiquimod-induced mouse psoriasis model and in human keratinocytes and macrophages stimulated by imiquimod.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-19
      DOI: 10.1016/j.jid.2021.06.029
       
  • Subclinical Liver Disease is Associated with Subclinical Atherosclerosis
           in Psoriasis: Results from Two Observational Studies

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      Authors: Alvaro Gonzalez-Cantero; Meron Teklu, Alexander V. Sorokin, Ronald Prussick, Jorge González-Cantero, Jose Luis Martin- Rodriguez, Nidhi Patel, Philip M. Parel, Grigory A. Manyak, Heather L. Teague, Justin A. Rodante, Andrew Keel, Cristina Pérez-Hortet, Ana I. Sanchéz-Moya, Natalia Jiménez, Asunción Ballester, Jorge Solis, Leticia Fernandez-Friera, María G. Barderas, Jorge L. Gonzalez-Calvin, Pedro Jaen, Martin P. Playford, Amit K. Dey, Joel M. Gelfand, Nehal N. Mehta
      Abstract: Psoriasis is associated with a higher risk of liver diseases. We investigated the impact of hepatic steatosis (European cohort) and hepatic inflammation (United States cohort) on subclinical atherosclerosis. In the European cohort (n=76 psoriasis participants and 76 controls), non-alcoholic fatty liver disease (NAFLD), assessed by the sonographic hepatorenal index (SHRI), was more prevalent in psoriasis than controls (61% vs 45%; p=.04). Psoriasis participants with NAFLD had a higher prevalence of subclinical atherosclerosis (ultrasonographic presence of plaque in femoral or carotid arteries) than psoriasis without NAFLD (61% vs 23%; p=.006) and controls with NAFLD (61% vs 32%; p
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-19
      DOI: 10.1016/j.jid.2021.05.034
       
  • PDL1 triggered by binding eIF3I contributes to the amelioration of
           diabetes-associated wound healing defects by regulating IRS4

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      Authors: Le Kuai; Yan-wei Xiang, Qi-long Chen, Yi Ru, Shuang-yi Yin, Wei Li, Jing-si Jiang, Ying Luo, Jian-kun Song, Bing Lu, Yue Luo, Bin Li
      Abstract: Persistent chronic inflammation and delayed epithelialization lead to stalled healing in diabetic ulcers (DUs). PDL1 shows anti-inflammatory and proliferative activities in healing defects, while its function in DU pathogenesis remains unknown. Lower levels of PDL1 were found in DU tissues, and exogenous PDL1 has therapeutic effects in healing process by accelerating re-epithelialization and attenuating prolonged inflammation, which contributed to the delayed wound closure. We detected the downstream effectors of PDL1 using transcriptional profiles, and screened the interacting proteins by IP-MS and Co-IP assays.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-19
      DOI: 10.1016/j.jid.2021.06.028
       
  • Extended T cell epitope landscape in Merkel cell polyomavirus large T and
           small T oncoproteins identified uniquely in cancer patients

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      Authors: Ulla Kring Hansen; Rikke Lyngaa, Dafina Ibrani, Candice Church, Monique Verhaegen, Andrzej Antoni Dlugosz, Jurgen Christian Becker, Per thor Straten, Paul Nghiem, Sine Reker Hadrup
      Abstract: TO THE EDITOR
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-19
      DOI: 10.1016/j.jid.2021.06.027
       
  • Nuclear IL-33 plays an important role in IL-31-mediated downregulation of
           filaggrin, keratin 1, and keratin 10 by regulating STAT3 activation in
           human keratinocytes

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      Authors: Xiuju Dai; Ken Shiraishi, Jun Muto, Ryo Utsunomiya, Hideki Mori, Masamoto Murakami, Koji Sayama
      Abstract: Interleukin (IL)-33, a chromatin-associated multifunctional cytokine, is implicated in the pathogenesis of atopic dermatitis (AD), an inflammatory skin disorder characterized by skin barrier dysfunction. IL-33 accumulates in the nuclei of epidermal keratinocytes in AD lesions. However, it is unclear whether nuclear IL-33 directly contributes to the pathogenesis of AD. IL-31, a pruritogenic cytokine primarily produced by T helper type 2 cells, is elevated in AD lesions and promotes AD development by suppressing keratinocyte differentiation and inducing itching.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-19
      DOI: 10.1016/j.jid.2021.05.033
       
  • Sensory re-innervation of human skin by human neural stem cell-derived
           peripheral neurons ex vivo

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      Authors: Jérémy Chéret; Ilaria Piccini, Jennifer Gherardini, Leslie Ponce, Marta Bertolini, Ralf Paus
      Abstract: To the editor, While the use of full-thickness human skin organ culture (hSOC) in pre-clinical research has many advantages compared to reconstructed so-called 3D skin “equivalents”, it is usually denervated (Zhou et al, 2018). Re-innervation of human skin ex vivo by sensory neurons derived from rat dorsal root ganglia (DRG) (Lebonvallet et al, 2012; Cheret et al, 2014; S1) combines cells/tissues from two very different species, and requires that rat nerve fibers (NFs), neuropeptides, neurotransmitters and neurotrophins communicate with cognate human receptors.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-19
      DOI: 10.1016/j.jid.2021.05.032
       
  • Uncovering the potential of PI3K inhibitors in cutaneous T cell lymphoma:
           insights from high throughput in vitro screenings

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      Authors: Amber Loren O. King; Fatima N. Mirza, Julia M. Lewis, Shiela Umlauf, Yulia Surosteva, Kacie R. Carlson, Francine M. Foss, Michael Girardi
      Abstract: We read with interest the article by Wu et al on combination inhibition of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC) using cutaneous T cell lymphoma (CTCL) patient-derived xenograft (PDX) models (Wu et al, 2021). We agree with Wu et al that the potential to harness PI3K inhibitors for advanced CTCL lies in the exploration of novel combination therapies. Herein, we share our relevant preclinical dataset suggesting that as single agents, PI3K inhibitors exhibited limited efficacy against CTCL with advanced stage.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-19
      DOI: 10.1016/j.jid.2021.04.035
       
  • Oncogenic Hedgehog-smoothened signaling depends on YAP1-TAZ/TEAD
           transcription to restrain differentiation in basal cell carcinoma

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      Authors: Yao Yuan; Natalia Salinas Parra, Qianming Chen, Ramiro Iglesias-Bartolome
      Abstract: Disruption of the transcriptional activity of the Hippo pathway members YAP1 and TAZ has become a major target for cancer treatment. However, detailed analysis of the effectivity and networks affected by YAP1/TAZ transcriptional targeting are limited. Here, we utilize TEADi, an inhibitor of the binding of YAP1 and TAZ with their main transcriptional target TEAD in a mouse model of basal cell carcinoma (BCC) to unveil the consequences of YAP1/TAZ transcriptional inhibition in cancer cells. Both TEADi and YAP1/TAZ knockdown lead to reduced proliferation and increased differentiation of mouse BCC driven by oncogenic Hedgehog-Smoothened (SmoM2) activity.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-19
      DOI: 10.1016/j.jid.2021.06.020
       
  • Antigen Processing, Presentation, and Tolerance: Role in Autoimmune Skin
           Diseases

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      Authors: Jörg Christoph Prinz
      Abstract: Autoreactive T cells pose a constant risk for the emergence of autoimmune skin diseases in genetically predisposed individuals carrying certain HLA risk alleles. Immune tolerance mechanisms are opposed by broad HLA-presented self-immunopeptidomes, a predefined repertoire of polyspecific TCRs, the continuous generation of new antibody specificities by somatic recombination of Ig genes in B cells, and heightened proinflammatory reactivity. Increased autoantigen presentation by HLA molecules, cross-activation of pathogen-induced T cells against autologous structures, altered metabolism of self-proteins, and excessive production of proinflammatory signals may all contribute to the breakdown of immune tolerance and the development of autoimmune skin diseases.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-19
      DOI: 10.1016/j.jid.2021.05.009
       
  • DNA methylation array identifies golli-MBP as a biomarker for the disease
           severity in childhood atopic dermatitis

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      Authors: Kuang-Den Chen; Ying-Hsien Huang, Mindy Ming-Huey Guo, Ling-Sai Chang, Chi-Hsiang Chu, Li-Feng Bu, Chiao-Lun Chu, Chih-Hung Lee, Shih-Feng Liu, Ho-Chang Kuo
      Abstract: In this study, we investigated the changes in the global methylation status and its functional relevance in childhood atopic dermatitis (AD). Differences in epigenome-scale methylation events in peripheral blood associated with childhood AD were screened using DNA methylation arrays of 24 AD patients compared to 24 control subjects (C).Of the 16,840 differentially methylated CpG regions between AD and C,> 97% CpG loci revealed hypomethylation in childhood AD patients. Among the globally hypomethylated loci, we identified two CpG clusters within the golli-mbp locus of the myelin basic protein (MBP) gene, which was functionally enriched by sub-network enrichment analysis (SNEA) as an orchestrator among associated genes.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-18
      DOI: 10.1016/j.jid.2021.06.025
       
  • HDAC1/2 control proliferation and survival in adult epidermis and
           pre-basal cell carcinoma via p16 and p53

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      Authors: Xuming Zhu; Matthew Leboeuf, Fang Liu, Marina Grachtchouk, John T. Seykora, Edward E. Morrisey, Andrzej A. Dlugosz, Sarah E. Millar
      Abstract: HDAC inhibitors show therapeutic promise for skin malignancies; however, the roles of specific HDACs in adult epidermal homeostasis and disease are poorly understood. We find that homozygous epidermal co-deletion of Hdac1 and Hdac2 in adult mouse epidermis causes reduced basal cell proliferation, apoptosis, inappropriate differentiation, and eventual loss of Hdac1/2-null keratinocytes. Hdac1/2 deficient epidermis displays elevated acetylated p53 and increased expression of the senescence gene p16.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-17
      DOI: 10.1016/j.jid.2021.05.026
       
  • Regulatory T Cells and Inflammatory Mediators in Autoimmune Disease

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      Authors: Victoire Gouirand; Ireneusz Habrylo, Michael D. Rosenblum
      Abstract: Regulatory T cells (Tregs) play a critical role in regulating tissue inflammation. Reduced Treg numbers and/or suppressive function contribute to autoimmune disease. Tregs can adopt the transcriptional programming of T helper (Th) type-1/2/17 cells to optimally suppress these subsets. Under specific conditions, these Th-like Tregs lose suppressive capacity and release proinflammatory cytokines to promote inflammation. This Treg plasticity depends on inflammatory mediators in the local environment.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-17
      DOI: 10.1016/j.jid.2021.05.010
       
  • Defining a role for GPCR/cAMP/Creb signaling in HFSC activation

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      Authors: M. Miranda; I. Avila, J. Esparza, Y. Shwartz, Y.C. Hsu, R. Berdeaux, W.E. Lowry
      Abstract: Manipulation of adrenergic signaling has been shown experimentally and clinically to affect hair follicle growth. Here we provide direct evidence that canonical cAMP/Creb signaling through adrenergic receptors can regulate HFSC activation and the hair cycle. We found that Creb activation is regulated through the hair cycle and coincides with HFSC activation. Both Isoproterenol and Procaterol, agonists of Adrenergic receptors show the capacity to activate HFSCs and the hair cycle in mice. Furthermore, deletion of Adrb2 receptor, which is thought to mediate sympathetic nervous system regulation of HFSCs, was sufficient to block HFSC activation.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-16
      DOI: 10.1016/j.jid.2021.05.031
       
  • Transient Induction of Fever in the Imiquimod C57BL/6 Mouse Model of
           Psoriasis-Like Disease Involves IL-1 and IL-6, but not IL-36

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      Authors: Shuang Sun; Laurie E. Kilpatrick, Liselotte E. Jensen
      Abstract: Psoriasis embodies a number of related chronic inflammatory skin conditions. Plaque psoriasis is the most common form and affects 1-3% of the population in many Western countries, while generalized pustular psoriasis (GPP) is a much rarer severe form. In addition to skin manifestations, GPP patients also exhibit several signs of systemic disease, including fever, elevated serum C-reactive protein levels and general malaise (Marrakchi et al., 2011, Onoufriadis et al., 2011). GPP is associated with mutations in the gene encoding the interleukin-36 (IL-36) receptor antagonist (IL-36Ra) (Marrakchi et al., 2011, Onoufriadis et al., 2011).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-16
      DOI: 10.1016/j.jid.2021.05.028
       
  • Deciphering mesenchymal drivers of human Dupuytren’s disease at
           single-cell level.

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      Authors: Ross Dobie; Chris C. West, Beth EP. Henderson, John R. Wilson-Kanamori, Dyana Markose, Laura J. Kitto, Jordan R. Portman, Mariana Beltran, Sadaf Sohrabi, Ahsan R. Akram, Prakash Ramachandran, Li Yenn Yong, Dominique Davidson, Neil C. Henderson
      Abstract: Dupuytren’s disease (DD) is a common, progressive fibroproliferative disease affecting the palmar fascia of the hands, causing fingers to irreversibly flex towards the palm with significant loss of function. Surgical treatments are limited, therefore effective new therapies for DD are urgently required. To identify key cellular and molecular pathways driving DD we employed single-cell RNA sequencing (scRNA-seq), profiling the transcriptomes of 35,250 human single cells from DD, non-pathogenic fascia, and healthy dermis.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-15
      DOI: 10.1016/j.jid.2021.05.030
       
  • Response to Marchetti et al.

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      Authors: Darrell S. Rigel; John W. Whitaker, Maral K. Skelsey, Gary Peck, Michael D. Howell, Burkhard Jansen
      Abstract: To the Editor, Recently, Marchetti et al. used decision curve analysis and hypothetical models of melanoma biopsy prevalence to retrospectively evaluate the clinical utility of the 2 Gene Expression Profile Pigmented Lesion Assay(PLA, DermTech, La Jolla, CA)(Marchetti et al. 2021). While the further evaluation of the PLA is appreciated, significant concerns exist regarding material flaws in Marchetti et al.’s analyses and characterizations. These include: (1) incorrectly characterizing the PLA as a ‘test for melanoma diagnosis’, (2) significant challenges within the hypothetical models used and the data input and interpretations employed, and (3) erroneous assumptions and implications that the social cost of not biopsying a melanoma is equivalent to performing an unneeded biopsy.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-14
      DOI: 10.1016/j.jid.2021.06.024
       
  • Response to Rigel et al./JID-2021-0347.R1

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      Authors: Michael A. Marchetti; Stephen W. Dusza
      Abstract: We thank Rigel et al for their interest in our study and the opportunity to clarify our findings.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-14
      DOI: 10.1016/j.jid.2021.06.023
       
  • Senescent progenitor cells in the skin of patients with cutaneous lupus
           erythematosus

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      Authors: Xiaoyan Wang; Gilles Diercks, Wietske M. Lambers, Johanna Westra, Hendrika Bootsma, Frans G.M. Kroese, Karina de Leeuw, Sarah Pringle
      Abstract: Cutaneous lupus erythematosus (CLE) is an autoimmune disease that can occur as isolated skin condition or as skin manifestation secondary to systemic autoimmune diseases like systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) (Kuhn and Landmann 2014; Wenzel 2019). CLE is commonly associated with type I and type III interferon-driven inflammation, with chronic discoid lupus erythematosus (CDLE) and subacute cutaneous lupus erythematosus (SCLE) as frequent subtypes (Wenzel 2019).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-14
      DOI: 10.1016/j.jid.2021.06.022
       
  • From your nose to your toes: A Review of SARS-CoV-2 Pandemic-associated
           Pernio

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      Authors: Lisa M. Arkin; John J. Moon, Jennifer M. Tran, Samira Asgari, Cliona O’Farrelly, Jean-Laurent Casanova, Edward W. Cowen, Jacqueline W. Mays, Anne Marie Singh, Beth A. Drolet, COVID Human Genetic Effort
      Abstract: Despite thousands of reported patients with pandemic-associated pernio, low rates of seroconversion and PCR positivity have defied causative linkage to SARS-CoV-2. Pernio in uninfected children is associated with monogenic disorders of excessive type 1 interferon (IFN-1) immunity, while severe COVID-19 pneumonia can result from insufficient IFN-1. Moreover, SARS-CoV-2 spike protein and robust IFN-1 response are seen in the skin of pandemic-associated pernio, suggesting an excessive innate immune skin response to SARS-CoV-2.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-14
      DOI: 10.1016/j.jid.2021.05.024
       
  • Human desmocollin 3-specific IgG antibodies are pathogenic in a humanized
           HLA-class II transgenic mouse model of pemphigus

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      Authors: C. Hudemann; R. Maglie, M. Llamazares, B. Beckert, D. Didona, R. Tikkanen, T. Schmitt, T. Hashimoto, J. Waschke, M. Hertl, R. Eming
      Abstract: Pemphigus is a potentially lethal autoimmune bullous skin disorder, which is associated with IgG autoantibodies against desmoglein 3 (Dsg3) and Dsg1. Notably, a subset of pemphigus patients presents with a similar clinical phenotype in the absence of anti-Dsg IgG, suggesting the presence of serum IgG reactive with desmosomal components other than Dsg1 or Dsg3. We and others have previously shown that such patients have serum IgG autoantibodies against desmocollin 3 (Dsc3), a component of desmosomes, that induce loss of keratinocyte adhesion ex vivo.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-12
      DOI: 10.1016/j.jid.2021.06.017
       
  • Deep Learning for Basal Cell Carcinoma Detection for Reflectance Confocal
           Microscopy.

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      Authors: Gabriele Campanella; Cristian Navarrete-Dechent, Konstantinos Liopyris, Jilliana Monnier, Saud Aleissa, Bramhteg Minas, Alon Scope, Caterina Longo, Pascale Guitera, Giovanni Pellacani, Kivanc Kose, Allan C. Halpern, Thomas J. Fuchs, Manu Jain
      Abstract: Basal cell carcinoma (BCC) is the most common skin cancer, with over 2 million cases diagnosed annually in the United States. Conventionally, BCC is diagnosed by naked eye examination and dermoscopy. Suspicious lesions are either removed or biopsied for histopathological confirmation, thus lowering the specificity of non-invasive BCC diagnosis. Recently, reflectance confocal microscopy (RCM), a non-invasive diagnostic technique that can image skin lesions at cellular level resolution, has shown to improve specificity in BCC diagnosis and reduced the number needed to biopsy by 2-to-3 times.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-12
      DOI: 10.1016/j.jid.2021.06.015
       
  • Activation of PKG restricts melanoma growth and invasion by interfering
           with the EGF/EGFR pathway

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      Authors: Marika Quadri; Antonella Comitato, Elisabetta Palazzo, Natascia Tiso, Andreas Rentsch, Giovanni Pellacani, Alessandra Marconi, Valeria Marigo
      Abstract: Drug resistance mechanisms still characterize metastatic melanoma, despite new treatments have been recently developed. Targeting of the cGMP/protein kinase G (PKG) pathway is emerging as a therapeutic approach in cancer research. In this study, we evaluated the anticancer effects of two polymeric linked dimeric (PDL) cGMP analogues able to bind and activate PKG, called PKG-activator (PA) 4 and 5. PA5 was identified as the most effective compound on melanoma cell lines as well as on patient-derived metastatic melanoma cells cultured as three-dimensional spheroids and in a zebrafish melanoma model.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-12
      DOI: 10.1016/j.jid.2021.06.011
       
  • Shifts in the skin bacterial and fungal communities of healthy children
           transitioning through puberty

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      Authors: Jin Park; Nicole H. Schwardt, Jay-Hyun Jo, Zhiwei Zhang, Valentina Pillai, Sheila Phang, Sheila M. Brady, Jessica A. Portillo, Margaret A. MacGibeny, Hai Liang, Meridith Pensler, Steven J. Soldin, Jack A. Yanovski, Julia A. Segre, Heidi H. Kong
      Abstract: Previous cross-sectional studies have shown that skin microbiomes in adults are distinct from children. However, the human skin microbiome in individuals as they sexually mature has not been studied as extensively. We performed a prospective, longitudinal study to investigate puberty-associated shifts in skin microbiota. Twelve healthy children were evaluated every 6-18 months for up to 6 years. Using 16S rRNA (V1-V3) and ITS1 amplicon sequencing analyzed with DADA2, we characterized the bacterial and fungal communities of 5 different skin and nares sites.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-09
      DOI: 10.1016/j.jid.2021.04.034
       
  • Neutrophils as Drivers of Immune Dysregulation in Autoimmune Diseases with
           Skin Manifestations

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      Authors: Shuichiro Nakabo; Jorge Romo-Tena, Mariana J. Kaplan
      Abstract: Dysregulation in the phenotype and function of neutrophils may play important roles in the initiation and perpetuation of autoimmune responses, including conditions affecting the skin. Neutrophils can have local and systemic effects on innate and adaptive immune cells as well as on resident cells in the skin, including keratinocytes (KCs). Aberrant formation/clearance of neutrophil extracellular traps (NETs) in systemic autoimmunity and chronic inflammatory diseases have been associated with the externalization of modified autoantigens in peripheral blood and tissues.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-09
      DOI: 10.1016/j.jid.2021.04.014
       
  • Pityriasis rubra pilaris response to IL-17A inhibition is associated with
           IL-17C and CCL20 protein levels

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      Authors: Jennifer L. Strunck; Brett Cutler, Barik Rajpal, Gail Kent, Dylan Haynes, Christina A. Topham, Alex G. Ortega-Loayza, Doris Yang, Zhiping Wang, Yuangang Liu, Pamela Cassidy, Teri M. Greiling
      Abstract: Pityriasis rubra pilaris (PRP) is a rare, severe inflammatory skin disease associated with high morbidity and debilitating effects on quality of life (Eastham et al., 2019, Ross et al., 2016). Classical features include follicular hyperkeratosis, erythematous plaques often progressing to erythroderma with “islands of sparing,” and waxy, palmoplantar keratoderma. The pathogenesis and etiology of PRP remain poorly understood. Small case series have shown dysregulation of the interleukin (IL)-23/IL-17 axis (Adnot-Desanlis et al., 2013, Feldmeyer et al., 2017, Nagai et al., 2020).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-08
      DOI: 10.1016/j.jid.2021.06.009
       
  • Pathogenic Activation and Therapeutic Blockage of Fc Alpha
           Receptor-Expressing Polymorphonuclear Leukocytes in IgA Pemphigus

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      Authors: Shirin Emtenani; Saeedeh Ghorbanalipoor, Sarah Mayer-Hain, Khalaf Kridin, Lars Komorowski, Christian Probst, Takashi Hashimoto, Hendri H. Pas, Kaja Męcińska-Jundziłł, Rafał Czajkowski, Andreas Recke, Cord Sunderkötter, Stefan W. Schneider, Jennifer E. Hundt, Detlef Zillikens, Enno Schmidt, Ralf J. Ludwig, Christoph M. Hammers
      Abstract: Pathomechanisms in IgA pemphigus are assumed to rely on Fc-dependent cellular activation by antigen-specific IgA autoantibodies, however, models for disease and more detailed pathophysiologic data are lacking. We here aimed to establish in vitro models of disease for IgA pemphigus, allowing to study effects of the interaction of anti-keratinocyte IgA with cell-surface Fc alpha receptors. Employing multiple in vitro assays, such as a skin cryosection assay and a human skin organ culture model, we here present mechanistic data for the pathogenesis of IgA pemphigus, mediated by anti-desmoglein 3 IgA autoantibodies.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-08
      DOI: 10.1016/j.jid.2021.06.007
       
  • No evident systemic terminal complement pathway activation in hidradenitis
           suppurativa

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      Authors: L.M. Prens; C.B. Ardon, K.R. van Straalen, H.H. van der Zee, M.A.J. Seelen, J.D. Laman, E.P. Prens, B. Horváth, J. Damman
      Abstract: In hidradenitis suppurativa (HS) lesional skin activation of both innate and adaptive immunity has been described, characterized by upregulation of a multitude of cytokines and complement components (Van der Zee et al., 2011). Higher levels of C5a and soluble C5b-9 (sC5b-9) in plasma of HS patients have been reported, indicating systemic late phase complement pathway activation in HS (Kanni et al., 2018). This formed the basis for two (ongoing) clinical trials, NCT03001622 and NCT03487276, targeting C5a and C5a receptor 1 in HS patients.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-08
      DOI: 10.1016/j.jid.2021.03.037
       
  • Solar simulated light induces cutaneous squamous cell carcinoma in inbred
           mice: a clinically relevant model to investigate T cell responses

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      Authors: Anngela C. Adams; Anne M. Macy, Kathylynn Saboda, Sally E. Dickinson, David J. Glembocki, Denise J. Roe, Karen Taraszka Hastings
      Abstract: More than one million cutaneous squamous cell carcinomas (cSCC) are diagnosed annually in the US (Rogers et al., 2015). The main causal factor of cSCC is UV exposure from sunlight, which is comprised of 95% UVA and 5% UVB at the Earth’s surface. UVA and UVB cause cyclobutane pyrimidine dimers in DNA and oxidative damage through the formation of reactive oxygen species. The ratio of cyclobutane pyrimidine dimers to oxidative DNA damage products is ∼800 times greater in UVB than UVA (Zhang et al., 1997).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-08
      DOI: 10.1016/j.jid.2021.06.005
       
  • Single-cell RNA-seq reveals lineage-specific regulatory changes of
           fibroblasts and vascular endothelial cells in keloids

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      Authors: Xuanyu Liu; Wen Chen, Qingyi Zeng, Baihui Ma, Zhujun Li, Tian Meng, Jie Chen, Nanze Yu, Zhou Zhou, Xiao Long
      Abstract: Keloids are a benign dermal fibrotic disorder with features similar to malignant tumors. keloids remain a therapeutic challenge and lack medical therapies, which is partially due to the incomplete understanding of the pathogenesis mechanism. We performed single-cell RNA-seq of 28,064 cells from keloid skin tissue and adjacent relatively normal tissue. Unbiased clustering revealed substantial cellular heterogeneity of keloid tissue, which included 21 clusters assigned to 11 cell lineages. We observed significant expansion of fibroblast and vascular endothelial cell subpopulations in keloids, reflecting their strong association with keloid pathogenesis.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-06
      DOI: 10.1016/j.jid.2021.06.010
       
  • CAMKK2 defines ferroptosis sensitivity of melanoma cells by regulating
           AMPK-Nrf2 pathway

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      Authors: Sijia Wang; Xiuli Yi, Zhenjie Wu, Sen Guo, Wei Dai, Huina Wang, Qiong Shi, Kang Zeng, Weinan Guo, Chunying Li
      Abstract: Melanoma is the most lethal skin cancer caused by malignant transformation of epidermal melanocyte. Recent progress in targeted therapy and immunotherapy has significantly improved the treatment outcome, but the survival of patients with advanced melanoma remains suboptimal. Ferroptosis, a cell death modality triggered by iron-dependent lipid peroxidation, reportedly participates in cancer pathogenesis and can mediate the effect of anti-PD-1 immunotherapy in melanoma. However, the detailed regulatory mechanism of ferroptosis remains far from understood.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-06
      DOI: 10.1016/j.jid.2021.05.025
       
  • Skin Sodium Accumulates in Psoriasis and Reflects Disease Severity

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      Authors: András Maifeld; Johannes Wild, Tine V. Karlsen, Natalia Rakova, Elisa Wistorf, Peter Linz, Rebecca Jung, Anna Birukov, Vladimir-Andrey Gimenez-Rivera, Nicola Wilck, Theda Bartolomaeus, Ralf Dechend, Markus Kleinewietfeld, Sofia K. Forslund, Andreas Krause, Georgios Kokolakis, Sandra Philipp, Björn E. Clausen, Anna Brand, Ari Waisman, Florian C. Kurschus, Joanna Wegner, Michael Schultheis, Friedrich C. Luft, Michael Boschmann, Marcus Kelm, Helge Wiig, Titus Kuehne, Dominik N. Müller, Susanne Karbach, Lajos Markó
      Abstract: Sodium can accumulate in the skin, at concentrations exceeding serum levels. High sodium environment can lead to pathogenic T helper (Th)17 cell expansion. Psoriasis is a chronic inflammatory skin disease in which interleukin (IL)-17-producing Th17 cells play a crucial role. In an observational study, we measured skin sodium content in psoriasis patients and age-matched healthy controls by 23Na-magnetic resonance imaging (MRI). Patients with a psoriasis area and severity index (PASI)>5 showed significantly higher sodium and water content in the skin, but not in other tissues, compared to those with lower PASI or healthy controls.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-05
      DOI: 10.1016/j.jid.2021.06.013
       
  • A PDZ Protein GIPC3 Positively Modulates Hedgehog Signaling and Melanoma
           Growth

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      Authors: Sathya Narayanan Patmanathan; Bing Teck Tong, Jia Hao Jackie Teo, Yong Zheng Jonathan Ting, Nguan Soon Tan, Siew Hoon Kenice Sim, Yng-Cun Ta, Wei-Meng Woo
      Abstract: The Hedgehog (Hh) pathway is essential for animal development but aberrant activation promotes cancer growth. Here we show that GIPC3, a PDZ domain-containing protein with putative adaptor protein function, positively modulates Hh target gene expression in normal fibroblasts and melanoma cells and supports melanoma tumor growth. Using overexpression and epistasis studies, we show that Gipc3 potentiates Hh transcriptional output and it modulates GLI-dependent transcription independently of Sufu. While we find GIPC3 protein does not interact with Hh pathway components, Ingenuity Pathway Analyses of GIPC3-interacting proteins identified by co-immunoprecipitation and mass spectrometry show an association with cancer pathogenesis.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-07-02
      DOI: 10.1016/j.jid.2021.04.033
       
  • The psoriatic non-lesional skin: a battlefield of constant fight between
           susceptibility and protective factors

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      Authors: Evelyn Kelemen; Renáta Bozó, Gergely Groma, Zsuzsanna Bata-Csörgő, Lajos Kemény, Judit Danis, Márta Széll
      Abstract: In the last two decades, large-scale gene-expression studies on psoriatic skin samples revealed that even though non-lesional skin is macroscopically identical to healthy skin, it harbors several molecular differences. Originally, these molecular differences were thought to represent susceptibility factors for plaque formation. However, we review here several factors of immune regulation and structural alteration that are specific for the non-lesional skin and serve as protective factors by counteracting plaque formation and contributing to the maintenance of the non-lesional phenotype.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-30
      DOI: 10.1016/j.jid.2021.05.020
       
  • Slow transcription of the 99a/let-7c/125b-2 cluster results in
           

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      Authors: Danna Sheinboim; Shivang Parikh, Roma Parikh, Amitai Menuchin, Guy Shapira, Oxana Kapitansky, Nadav Elkoshi, Shmuel Ruppo, Lital Shaham, Tamar Golan, Sharona Elgavish, Yuval Nevo, Rachel E. Bell, Hagar Malcov, Noam Shomron, Jeffrey W. Taub, Shai Izraeli, Carmit Levy
      Abstract: Almost half of human miRNAs are encoded in clusters. Although transcribed as a single unit, the levels of individual mature miRNAs often differ. The mechanisms underlying differential biogenesis of clustered miRNAs and the resulting physiological implications are mostly unknown. Here, we report that the melanoma master transcription regulator MITF regulates the differential expression of the 99a/let-7c/125b-2 cluster by altering the distribution of RNA polymerase II (Pol-II) along the cluster. We discovered that MITF interacts with TRIM28, a known inhibitor of Pol-II transcription elongation, at the let-7c region resulting in Pol-II pausing and causing its elevated expression, whereas low levels of Pol-II occupation over miR-99a and miR-125b-2 regions decreases their biogenesis.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-25
      DOI: 10.1016/j.jid.2021.03.036
       
  • Hair-follicle mesenchymal stem-cell activity during homeostasis and wound
           healing

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      Authors: Emil Aamar; Efrat Avigad Laron, Wisal Asaad, Sarina Harshuk-Shabso, David Enshell-Seijffers
      Abstract: The mesenchymal components of the hair follicle, the dermal papilla (DP) and dermal sheath (DS), are maintained by hair-follicle dermal stem cells (hfDSCs), but the position of this stem cell population throughout the hair cycle, its contribution to the maintenance of the dermis and the existence of a migratory axis from the DP to the dermis remain unclear. Here we show that during homeostasis DP and DS cells are confined to their compartments, and during the regression phase of the hair cycle, some undergo apoptosis and subsequently are internalized by nearby adipocytes.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-21
      DOI: 10.1016/j.jid.2021.05.023
       
  • Immunophenotypic analysis reveals differences in circulating immune cells
           in peripheral blood of segmental and non-segmental vitiligo patients

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      Authors: Marcella Willemsen; Nicoline F. Post, Nathalie OP. van Uden, Vidhya S. Narayan, Saskia Chielie, E Helen Kemp, Marcel W. Bekkenk, Rosalie M. Luiten
      Abstract: Accumulating studies have indicated immune-based destruction of melanocytes in both segmental vitiligo (SV) and non-segmental vitiligo (NSV). Whereas SV often occurs unilaterally during childhood and stabilizes after an initial period of activity, the disease course of NSV is usually slowly progressive, with new lesions occurring bilaterally during life. This suggests involvement of distinct pathophysiology pathways, specifically increased systemic immune activation in NSV patients, but not in SV patients.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-21
      DOI: 10.1016/j.jid.2021.05.022
       
  • Mechanisms of Photosensitivity in Autoimmunity

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      Authors: Shannon N. Estadt; Mitra P. Maz, Jon Musai, J. Michelle Kahlenberg
      Abstract: Aberrant responses to UV light frequently lead to the formation of skin lesions and the activation of systemic inflammation in some autoimmune diseases, especially systemic lupus erythematosus. Whereas the effects of UV light on the skin have been studied for decades, only recently have some of the mechanisms that contribute to abnormal responses to UV light in patients with autoimmune diseases been uncovered. This review will discuss the biology of UV in the epidermis and discuss the abnormal epidermal and inflammatory mechanisms that contribute to photosensitivity.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-21
      DOI: 10.1016/j.jid.2021.05.007
       
  • Increased risk of skin cancer in 1851 long-term retinoblastoma survivors

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      Authors: Ruth A. Kleinerman; Sara J. Schonfeld, David H. Abramson, Jasmine H. Francis, Johanna M. Seddon, Lindsay M. Morton, Margaret A. Tucker
      Abstract: Hereditary retinoblastoma patients are at risk for developing cutaneous melanoma, but little is known about the role of sun exposure or other factors, and incidence of non-melanoma skin cancer (NMSC) is poorly understood. We investigated the incidence of melanoma and NMSC in a cohort of 1851 white, long-term retinoblastoma survivors (1020 hereditary and 831 nonhereditary) diagnosed from 1914-2006. During follow-up through 2016, 33 hereditary and 7 nonhereditary survivors developed melanoma, and 26 hereditary and 9 nonhereditary survivors developed NMSC.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-18
      DOI: 10.1016/j.jid.2021.05.021
       
  • Gene expression profiling in skin reveals strong similarities between
           subacute and chronic cutaneous lupus that are distinct from lupus
           nephritis

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      Authors: Wei-Che C. Ko; Li Li, Taylor R. Young, Riley E. McLean-Mandell, April C. Deng, Vijay K. Vanguri, Karen Dresser, John E. Harris
      Abstract: Subacute cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE) are represented in the majority of cutaneous lupus subtypes, each of which has variable implications for systemic manifestations such as lupus nephritis.On dermatologic exam, SCLE and CCLE are distinct. However, it is often difficult to diagnose the subtype from histology alone. Our study utilized whole-genome microarray expression analysis on human skin samples of SCLE, CCLE, and healthy controls, along with human samples of lupus nephritis and normal kidney tissue to compare cutaneous lupus subtypes to each other, as well as lupus nephritis.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-17
      DOI: 10.1016/j.jid.2021.04.030
       
  • CD1-Restricted T Cells in Inflammatory Skin Diseases

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      Authors: Samantha Genardi; Eva Morgun, Chyung-Ru Wang
      Abstract: Autoimmunity results from the breaking of immune tolerance, leading to inflammation and pathology. Although well studied in the conventional T-cell field, the role of nonconventional T cells in autoimmunity is less understood. CD1-restricted T cells recognize lipid antigens rather than peptide antigens and have been implicated in various autoimmune skin conditions, including psoriasis and atopic dermatitis. In this review, we will discuss the self-lipids that CD1-restricted T cells recognize and how these T cells become aberrantly regulated in pathogenic skin conditions.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-12
      DOI: 10.1016/j.jid.2021.03.033
       
  • Safety, Tolerability, and Activity of ALXN1830 Targeting the Neonatal Fc
           Receptor in Chronic Pemphigus

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      Authors: Victoria P. Werth; Donna A. Culton, Josef S.S. Concha, James S. Graydon, Laurence J. Blumberg, Joyce Okawa, Michal Pyzik, Richard S. Blumberg, Russell P. Hall
      Abstract: Pemphigus is a debilitating immunoglobulin G (IgG)-mediated autoimmune disease in need of better tolerated, more targeted and rapid onset therapies. ALXN1830 is a humanized IgG4 antibody that blocks neonatal Fc receptor (FcRn) interactions with IgG. A multicenter, open-label safety and tolerability phase 1b/2 trial (NCT03075904) was conducted in North America from July 2017 to January 2019 and included patients aged ≥ 18 years with a confirmed diagnosis of pemphigus (vulgaris or foliaceus) and active disease.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-11
      DOI: 10.1016/j.jid.2021.04.031
       
  • Chikungunya virus envelope protein E2 provides a vector for targeted
           antigen delivery to human dermal CD14+ dendritic cells.

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      Authors: Adrien Brulefert; Melanie Kraemer, Marie Cumin, Amandine Selle, Astrid Hoste, Hans-Henrik Gad, Julia Rühl, Jean-Baptiste Madinier, Olivier Chaloin, Christian Münz, Philippe Desprès, Christopher George Mueller, Vincent Flacher
      Abstract: Therapeutic modulation of human cutaneous antigen-presenting cells (APCs) that control the fate of T cells represents an interesting option for immunotherapy. As they capture glycosylated proteins via C-type lectins, lectin-targeting antibodies have been used to specifically convey antigens to APCs (Romani et al., 2012;Stoitzner et al., 2014;Kastenmuller et al., 2014). Beyond potential therapeutic applications, APC-targeting strategies can be harnessed to acquire fundamental knowledge about their function (Flacher et al.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-10
      DOI: 10.1016/j.jid.2021.04.027
       
  • An in vitro model of avian skin reveals evolutionarily conserved
           transcriptional regulation of epidermal barrier formation

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      Authors: Julia Lachner; Sophia Derdak, Veronika Mlitz, Tanja Wagner, Karin Brigit Holthaus, Florian Ehrlich, Michael Mildner, Erwin Tschachler, Leopold Eckhart
      Abstract: The function of the skin as a barrier against a dry environment evolved in a common ancestor of terrestrial vertebrates such as mammals and birds. However, it is unknown which elements of the genetic program of skin barrier formation are evolutionarily ancient and conserved. Here, we determined the transcriptomes of chicken keratinocytes grown in monolayer culture and in an organotypic model of avian skin. The differentiation-associated changes in global gene expression were compared to previously published transcriptome changes of human keratinocytes cultured under equivalent conditions.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-08
      DOI: 10.1016/j.jid.2021.04.029
       
  • UDP-GlcNAc-1-phosphotransferase is a clinically important regulator of
           human and mouse hair pigmentation

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      Authors: Stephan Tiede; Jennifer E. Hundt, Ralf Paus
      Abstract: UDP-GlcNAc-1-phosphotransferase, a product of two separate genes (GNPTAB, GNPTG), is essential for sorting and transport of lysosomal enzymes to lysosomes. GNPTAB gene defects cause extracellular missorting of lysosomal enzymes resulting in lysosomal storage diseases, namely mucolipidosis (ML) type II, which is associated with hair discoloration. Yet, the physiological functions of GNPTAB in the control of hair follicle (HF) pigmentation remain unknown. To elucidate these, we have silenced GNPTAB- in organ-cultured human HFs as a human ex vivo-model for MLII.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-08
      DOI: 10.1016/j.jid.2021.04.028
       
  • Genotype-structurotype-phenotype correlations in pachyonychia congenita
           patients

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      Authors: Tiffany T. Wu; Sherif A. Eldirany, Christopher G. Bunick, Joyce M.C. Teng
      Abstract: Pachyonychia congenita (PC) is a genetic disorder of keratin that presents with nail dystrophy, painful palmoplantar keratoderma, and other clinical manifestations. We investigated genotype-structurotype-phenotype correlations seen with mutations in keratin genes (KRT6A, KRT6B, KRT6C, KRT16, KRT17) and utilized protein structure modeling of high frequency mutations to examine the functional importance of keratin structural domains in PC pathogenesis. Participants of the International PC Research Registry underwent genetic testing and completed a standardized survey on their symptoms.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-08
      DOI: 10.1016/j.jid.2021.03.035
       
  • Genotype-Phenotype Correlation in Trichilemmal Cysts

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      Authors: Ahmed Yousaf; Rachel Tallman, Steven Katzman, Chad Brady, Wei Feng, Michael S. Kolodney
      Abstract: Trichilemmal cysts (TCs) present both in autosomal dominant pattern and sporadic patterns (Friedrich and Wilczak, 2019, Seidenari et al., 2013). Recently, Horer (Hörer et al., 2019) and later ourselves (Kolodney et al., 2020) independently demonstrated that the p.Ser460Leu PLCD1 variant (NM_006225.4:c.1379 G > A, rs75495843) was the most common risk allele for TCs. A somatic ser745leu PLCD1 mutation was also present in all familial TC examined. Surprisingly, a ser745leu somatic mutation was always on the same chromosome as the germline p.Ser460Leu variant, in contradiction to the dogma of Knudson’s “two hit” hypothesis (Knudson, 1971).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-07
      DOI: 10.1016/j.jid.2021.05.018
       
  • Molecular genetic dissection of inflammatory linear verrucous epidermal
           naevus leads to successful targeted therapy

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      Authors: Melissa Riachi; Satyamaanasa Polubothu, Paulina Stadnik, Hughes Connor, Sara Barberan Martin, Carolyn R. Charman, Iek Leng Cheng, Karolina Gholam, Olumide Ogunbiyi, David G. Paige, Neil J. Sebire, Alan Pittman, Wei-Li Di, Veronica A. Kinsler
      Abstract: Inflammatory linear verrucous epidermal naevus (ILVEN) is a rare skin condition. Classically it presents at birth or within the first year of life, frequently progressing during early childhood. Diagnostic criteria are erythematous verrucous hyperkeratosis in a fine and whorled Blaschko-linear pattern, intense pruritus, early age of onset, histological features, and resistance to treatment(Morag and Metzker, 1985). The cause of ILVEN has been unknown, however a single case of mosaicism in gene GJA1 has recently been reported (Umegaki-Arao et al., 2017).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-07
      DOI: 10.1016/j.jid.2021.02.765
       
  • Glucagon-like peptide-1 analogues and sodium-glucose co-transporter-2
           inhibitors do not increase risk of bullous pemphigoid

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      Authors: Outi Varpuluoma; Jari Jokelainen, Laura Huilaja, Kaisa Tasanen
      Abstract: The association of bullous pemphigoid (BP) and dipeptidyl peptidase-4 inhibitors (DPP-4i) used for diabetes mellitus (DM) has recently attracted special interest in the field of BP research. (Nishie and Tasanen, 2019;Varpuluoma et al., 2018a). However, other diabetes drugs have been studied to a lesser extent in this context. In our previous case-control study of 3397 BP patients diagnosed in Finland between 1997 and 2013, we did not find increased risk of BP associated with oral DM drugs other than DPP-4is (Varpuluoma et al., 2018b).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-07
      DOI: 10.1016/j.jid.2021.05.015
       
  • RIP1-mediated necroptosis facilitates oxidative stress-induced melanocyte
           death offering insight into vitiligo

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      Authors: Bowei Li; Xiuli Yi, Tongtian Zhuang, Shaolong Zhang, Shuli Li, Yuqi Yang, Tingting Cui, Jiaxi Chen, Yuqian Chang, Tianwen Gao, Chunying Li, Ling Liu
      Abstract: Vitiligo is a common depigmentation disease characterized by the melanocyte death which is attributed to various mechanisms such as apoptosis and autoimmune destruction. However, whether necroptosis, a newly discovered way of cell death, plays a key role in the pathogenesis of vitiligo is still elusive has not been well studied. In this study, we found that necroptosis markers including phosphorylated receptor-interacting protein 3 (p-RIP3) and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) were positive in melanocytes from vitiligo perilesional skins, which supported the existence of necroptosis in vitiligo.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-04
      DOI: 10.1016/j.jid.2020.06.042
       
  • XENOBIOTIC CONSTITUTIVE ANDROSTANE RECEPTOR (CAR) IS HIGHLY INDUCED IN
           PSORIASIS AND PROMOTES KERATINOCYTE PROLIFERATION

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      Authors: Baochang Lai; Xinya Xie, Fan Li, Qi Cui, Erle Dang, Wenhuan Luo, Ning Wang, Yan Zheng, Gang Wang, Lei Xiao, Nanping Wang
      Abstract: Psoriasis is a chronic inflammatory skin disease with abnormal epidermal proliferation. Xenobiotics contribute to the pathogenesis of psoriasis. The mechanism linking xenobiotic stimuli with epidermal proliferation remains largely unknown. Here, we investigated a role of constitutive androstane receptor (CAR), a nuclear receptor (NR1I3) responsible for xenobiotics detoxification. We showed that CAR and its target genes were induced in the lesions from psoriasis patients and imiquimod (IMQ)-treated mice.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-04
      DOI: 10.1016/j.jid.2021.05.017
       
  • Golimumab for the Treatment of Hidradenitis Suppurativa in Patients with
           Previous Tumor Necrosis Factor-Alpha Treatment Failure

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      Authors: Maria del Mar Melendez-Gonzalez; Judy Hamad, Christopher Sayed
      Abstract: II. Letter
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-04
      DOI: 10.1016/j.jid.2021.04.026
       
  • Evidence for lysosomal dysfunction within the epidermis in psoriasis and
           atopic dermatitis

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      Authors: Kim Klapan; Živa Frangež, Nikita Markov, Shida Yousefi, Dagmar Simon, Hans-Uwe Simon
      Abstract: Atopic dermatitis (AD) and psoriasis (PS) are frequent chronic inflammatory skin diseases. Autophagy plays a substantial role in the homeostasis of the organism. Loss or impairment of autophagy is associated with multiple diseases. To investigate the possibility that autophagy plays a role in AD and PS, we investigated the levels of key autophagy-related proteins (ATGs) in human skin specimens as well as in primary human epidermal keratinocytes exposed to inflammatory stimuli in vitro. While TNF-α facilitated the induction of autophagy in an initial phase, it reduced the levels and enzymatic activities of lysosomal cathepsins in later time periods resulting in autophagy inhibition.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-03
      DOI: 10.1016/j.jid.2021.05.016
       
  • 83JAK-STAT inhibition mediates romidepsin and mechlorethamine synergism in
           Cutaneous T-cell Lymphoma

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      Authors: Jose R. Cortes; Christina C. Patrone, S. Aidan Quinn, Y. Gu, Marta Sanchez-Martin, Adam Mackey, Anisha Cooke, Bobby B. Shih, Anouchka P. Laurent, Megan H. Trager, Adolfo A. Ferrando, Larisa J. Geskin, Teresa Palomero
      Abstract: Sézary Syndrome (SS) is an aggressive and disseminated form of Cutaneous T-cell lymphoma (CTCL) associated with dismal prognosis in which the histone deacetylase inhibitor romidepsin, has shown remarkable activity as a single agent. However, clinical responses to romidepsin are typically transient, highlighting the need for more effective therapies. Here, we show synergistic anti-lymphoma effects of romidepsin in combination with mechlorethamine, an alkylating agent, in CTCL cell lines and primary samples with strong antitumor effects in an in vivo model of SS.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-02
      DOI: 10.1016/j.jid.2021.04.023
       
  • Role of Prostaglandin E-major Urinary Metabolite Levels in Identifying the
           Phenotype of Pachydermoperiostosis

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      Authors: Mami Ishibashi; Tomohiro Oiwa, Takashi Nomura, Yoshiaki Yoshikawa, Hironori Niizeki, Kenji Kabashima
      Abstract: Pachydermoperiostosis (PDP) is an autosomal recessive hereditary disease, that has three diagnostic features: digital clubbing, periostosis, and pachydermia including cutis verticis gyrata (CVG) (Castori et al., 2005). CVG is a condition in which folds of the hypertrophic scalp skin create a cerebriform appearance. The phenotypic spectrum of PDP has been categorized into three distinct forms. First, the complete form involves all three major symptoms including CVG. Second, the incomplete form has all three symptoms, but solely lacks CVG.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-01
      DOI: 10.1016/j.jid.2021.04.025
       
  • Polygenic Risk Scores Stratify Keratinocyte Cancer Risk among Solid Organ
           Transplant Recipients with Chronic Immunosuppression in a High Ultraviolet
           Radiation Environment.

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      Authors: Mathias Seviiri; Matthew H. Law, Jue Sheng Ong, Puya Gharahkhani, Dale R. Nyholt, Peter Hopkins, Daniel Chambers, Scott Campbell, Nicole M. Isbel, H. Peter Soyer, Catherine M. Olsen, Jonathan J. Ellis, David C. Whiteman, Adele C. Green, Stuart MacGregor
      Abstract: Solid organ transplant recipients (SOTRs) have elevated risks for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), especially in high ultraviolet (UV) radiation environments. We assessed whether polygenic risk scores (PRSs) can improve prediction of BCC and SCC risks and multiplicity over and above traditional risk factors in SOTRs in a high UV setting. We built PRSs for BCC (N=594,881) and SCC (N=581,431) using UK Biobank and 23andMe datasets, validated them in the Australian QSkin Cohort (N>6,300) and applied them in SOTRs in the STAR Cohort from Queensland, Australia, a high UV environment.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-01
      DOI: 10.1016/j.jid.2021.03.034
       
  • The XBP1-MARCH5-MFN2 axis confers ER stress resistance by coordinating
           mitochondrial fission and mitophagy in melanoma

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      Authors: Huina Wang; Xiuli Yi, Sen Guo, Sijia Wang, Jinyuan Ma, Tao Zhao, Qiong Shi, Yangzi Tian, Hao Wang, Lintao Jia, Tianwen Gao, Chunying Li, Weinan Guo
      Abstract: Melanoma cells are relatively resistant to ER stress, which contributes to tumor progression under stressful conditions and renders tolerance to ER stress-inducing therapeutic agents. Mitochondria are tightly interconnected with ER. However, whether mitochondria play a role in regulating ER stress resistance in melanoma remains elusive. Herein, we reported that the XBP1-MARCH5-MFN2 axis conferred ER stress resistance by coordinating mitochondrial fission and mitophagy in melanoma. Our integrative bioinformatics first revealed that the down-regulation of mitochondrial genes was highly correlated with UPR activation in melanoma.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-25
      DOI: 10.1016/j.jid.2021.03.031
       
  • A Genome-Wide Association Study Finds Variants at 2p21 Associated with
           Self-Reported Sensitive Skin in the Han Chinese population

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      Authors: Bingjie Li; Xiyang Cai, Lizhong Wang, Jiarui Li, Ying Zou, Gang Chen, Sijia Wang
      Abstract: Sensitive skin is defined by the occurrence of unpleasant sensations(e.g. stinging, burning, pain, pruritus, tingling) in response to various stimuli(e.g. cosmetics, temperature variation, emotion) that generally should not provoke such sensations(Brenaut et al., 2020, Misery et al., 2017). The face tends to be the most common site of skin sensitivity due to its rich innervation and its multiple types of contacted irritator. Facial sensitive skin affects around 55-57% of the Asian population, but varies substantially among countries and studies(Kamide et al., 2013, Kim et al., 2018).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-19
      DOI: 10.1016/j.jid.2021.04.021
       
  • ANTIMICROBIAL PEPTIDE LL-37 DRIVES ROSACEA-LIKE SKIN INFLAMMATION IN AN
           NLRP3-DEPENDENT MANNER

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      Authors: Sung-Hyun Yoon; Inhwa Hwang, Eunju Lee, Hyo-Joung Cho, Ju Hee Ryu, Tae-Gyun Kim, Je-Wook Yu
      Abstract: Rosacea is a chronic inflammatory skin disease characterized by immune response-dependent erythema and pustules. Although the precise etiology of rosacea remains elusive, its pathogenesis is reportedly associated with an increased level of antimicrobial peptide LL-37. However, molecular mechanisms underlying the progression of rosacea via LL-37 remain poorly understood. Here, we examined the potential role of LL-37 in rosacea-like skin inflammatory phenotypes at a molecular level. Our in vitro data demonstrated that LL-37 promotes NLRP3-mediated inflammasome activation in lipopolysaccharide-primed macrophages, indicated by the processing of caspase-1 and interleukin-1β.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-03-17
      DOI: 10.1016/j.jid.2021.02.745
       
  • Photoprotection of the Skin from Visible Light‒Induced Pigmentation:
           Current Testing Methods and Proposed Harmonization

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      Authors: Henry W. Lim; Indermeet Kohli, Corinne Granger, Carles Trullàs, Jaime Piquero-Casals, Mridvika Narda, Philippe Masson, Jean Krutmann, Thierry Passeron
      First page: 2569
      Abstract: Visible light (VL) can induce pigmentary alterations, especially in dark-skinned individuals, and exacerbate photodermatoses and pigmentary disorders. Currently, there is no standardized method for assessing sunscreen protection against VL. On the basis of a critical review of published in vitro and in vivo methods, a VL photoprotection assessment method based on pigmentation is proposed.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-07
      DOI: 10.1016/j.jid.2021.03.012
       
  • DECREASED CALCIUM SENSING RECEPTOR EXPRESSION CONTROLS CALCIUM SIGNALING
           AND CELL-TO-CELL ADHESION DEFECTS IN AGED SKIN

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      Authors: Anna Celli; Chia-Ling Tu, Elise Lee, Daniel D. Bikle, Theodora M. Mauro
      First page: 2577
      Abstract: The Ca2+-sensing receptor (CaSR) drives essential Ca2+ and E-cadherin-mediated processes in the epidermis, including differentiation (Komuves et al., 2002), cell-to-cell adhesion (Tu et al., 2008) and epidermal barrier homeostasis in cells and young adult mice (Tunggal et al., 2005; Tu et al., 2012; Tu et al., 2019). We now report that decreased CaSR expression leads to impaired Ca2+ signal propagation in aged (>22 months) mouse epidermis and (>79 years donor age) human keratinocytes. Baseline cytosolic Ca2+ concentrations were higher, and capacitive Ca2+ entry was lower in aged vs.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-04-13
      DOI: 10.1016/j.jid.2021.03.025
       
  • Dapsone Suppresses Disease in Preclinical Murine Models of Pemphigoid
           Diseases

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      Authors: Sripriya Murthy; Paul Schilf, Sabrina Patzelt, Markus Thieme, Mareike Becker, Lasse Kröger, Tabea Bremer, Aleksandra Derenda-Hell, Lea Knebel, Francesca Fagiani, Saleh M. Ibrahim, Enno Schmidt, Detlef Zillikens, Christian D. Sadik
      First page: 2587
      Abstract: Epidermolysis bullosa acquisita (EBA) and mucous membrane pemphigoid (MMP) are autoimmune blistering diseases characterized by mucocutaneous blisters elicited by an autoantibody-mediated immune response against specific proteins of the epidermal basement membrane.The antibiotic dapsone is frequently used to treat both diseases, but its therapeutic effectiveness is uncertain, and its mode of action in these diseases is largely unknown. We evaluated the effect of dapsone in antibody transfer mouse models of EBA and MMP, which do not allow drawing conclusions on clinical treatment regimens but can be instrumental to partially uncover the mode(s) of action of dapsone in these diseases.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-21
      DOI: 10.1016/j.jid.2021.04.009
       
  • International increases in Merkel cell carcinoma incidence rates between
           1997 and 2016

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      Authors: Catherine M. Olsen; Nirmala Pandeya, David C. Whiteman
      First page: 2596
      Abstract: Relatively little is known about the epidemiology of Merkel cell carcinoma (MCC) with regards to international trends in incidence, specifically relating to differences by age, sex and anatomic site. We examined trends in sex-specific incidence of MCC in the United States, Australia, New Zealand, Scotland and Norway over a 20-year period (1997-2016), as well as site-specific incidence trends in the US. We used Joinpoint regression models to estimate the average annual percentage change (AAPC) in incidence.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-04-28
      DOI: 10.1016/j.jid.2021.04.007
       
  • LAMININ 332 IS INDISPENSABLE FOR HOMEOSTATIC EPIDERMAL DIFFERENTIATION
           PROGRAMS

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      Authors: Raneem Tayem; Catherin Niemann, Monika Pesch, Jessica Morgner, Carien M. Niessen, Sara A. Wickström, Monique Aumailley
      First page: 2602
      Abstract: The skin epidermis is attached to the underlying dermis by a laminin 332-rich basement membrane. Consequently, loss of laminin 332 leads to the severe blistering disorder epidermolysis bullosa junctionalis in human and animals. Due to the indispensable role of laminin 332 in keratinocyte adhesion in vivo, the severity of the disease has limited research into other functions of the protein. We have conditionally disrupted laminin 332 expression in basal keratinocytes of adult mice. Although blisters develop along the interfollicular epidermis, hair follicle basal cells provide sufficient anchorage of the epidermis to the dermis, making inducible deletion of the lama3 gene compatible with life.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-06
      DOI: 10.1016/j.jid.2021.04.008
       
  • Low threshold for cutaneous allergen sensitization but no spontaneous
           dermatitis or atopy in filaggrin-deficient mice

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      Authors: Lina Muhandes; Maria Chapsa, Martin Pippel, Rayk Behrendt, Yan Ge, Andreas Dahl, Buqing Yi, Alexander Dalpke, Sylke Winkler, Michael Hiller, Sebastien Boutin, Stefan Beissert, Rolf Jessberger, Padraic G. Fallon, Axel Roers
      First page: 2611
      Abstract: Loss of filaggrin (FLG) causes Ichthyosis vulgaris. Reduced filaggrin expression compromises epidermal barrier function and is associated with atopic dermatitis, allergy and asthma. The flaky tail mouse harbors two mutations that affect the skin barrier, Flgft, resulting in hypomorphic FLG expression, and Tmem79matted inactivating transmembrane protein 79. Mice defective only for Tmem79 featured dermatitis and systemic atopy, but also Flgft/ft BALB/c congenic mice developed eczema, high IgE and spontaneous asthma, suggesting that Flg protects from atopy.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-04-21
      DOI: 10.1016/j.jid.2021.02.763
       
  • Triangulating molecular evidence to prioritize candidate causal genes at
           established atopic dermatitis loci

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      Authors: Maria K. Sobczyk; Tom G. Richardson, Verena Zuber, Josine L. Min, Tom R. Gaunt, Lavinia Paternoster, eQTLGen Consortium, BIOS Consortium, GoDMC
      First page: 2620
      Abstract: Genome-wide association studies for atopic dermatitis (AD) have identified 25 reproducible loci. We attempt to prioritize candidate causal genes at these loci using extensive molecular resources compiled into a bioinformatics pipeline.We identified a list of 103 molecular resources for AD aetiology, including expression, protein and DNA methylation QTL datasets in skin or immune-relevant tissues which were tested for overlap with GWAS signals. This was combined with functional annotation using regulatory variant prediction, and features such as promoter-enhancer interactions, expression studies and variant fine-mapping.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-04-23
      DOI: 10.1016/j.jid.2021.03.027
       
  • Functional Mapping of Genetic Interactions between Human Leukocyte Antigen
           (HLA)-Cw6 and Late Cornified Envelope 3A in Psoriasis

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      Authors: Aditi Chandra; Shantanab Das, Sayani Mazumder, Swapan Senapati, Gobinda Chatterjee, Raghunath Chatterjee
      First page: 2630
      Abstract: Functional studies to delineate the molecular mechanisms of causal genetic variants are the main focus in the post-GWAS era. Previous GWASs have identified more than 50 susceptibility loci associated with psoriasis. Functional understanding of the biology underlying the disease risk of most of these associated loci are unclear. Here, we identified a regulatory SNP at the putative enhancer of Late cornified envelope (LCE)-3A gene within the epidermal differentiation complex that showed epistatic interaction with the HLA-Cw6.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-21
      DOI: 10.1016/j.jid.2021.04.020
       
  • Genomic Association of Chronic Idiopathic Anhidrosis to a Potassium
           Channel Subunit in a Large Animal Model

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      Authors: Laura Patterson Rosa; Neely Walker, Martha Mallicote, Robert J. MacKay, Samantha A. Brooks
      First page: 2639
      Abstract: Like humans, the horse relies predominantly on evaporation of sweat from the skin surface to dissipate excess body heat. Loss of the sweat response, or anhidrosis, can result in life-threatening hyperthermia. Anhidrosis occurs more frequently in some breeds, as well as has an increased frequency among individuals with a family history, suggesting a heritable component to the pathology.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-31
      DOI: 10.1016/j.jid.2021.05.014
       
  • Nuclear IL-33 plays an important role in the suppression of filaggrin,
           loricrin, keratin 1, and keratin 10 by IL-4 and IL-13 in human
           keratinocytes

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      Authors: Xiuju Dai; Ryo Utsunomiya, Ken Shiraishi, Hideki Mori, Jun Muto, Masamoto Murakami, Koji Sayama
      First page: 2646
      Abstract: IL-33 is a chromatin-associated multifunctional cytokine implicated in the pathogenesis of atopic dermatitis (AD), an inflammatory skin disorder characterized by skin barrier dysfunction. The previous reports show that IL-33 is highly detected in the nucleus of epidermal keratinocytes in AD lesions compared to unaffected or normal skin. However, it is unclear whether intracellular IL-33 directly contributes to the pathogenesis of AD. Th2 cytokines IL-4 and IL-13 that are elevated in AD lesions suppress keratinocyte differentiation to impair skin barrier function.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-04-15
      DOI: 10.1016/j.jid.2021.04.002
       
  • Cyclin-Dependent Kinase 7 Promotes Th17/Th1 Cell Differentiation in
           Psoriasis by Modulating Glycolytic Metabolism

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      Authors: Yiting Lin; Ke Xue, Qingyang Li, Zhenhua Liu, Zhenlai Zhu, Jiaoling Chen, Erle Dang, Lei Wang, Weigang Zhang, Gang Wang, Bing Li
      First page: 2656
      Abstract: Excessive activation of CD4+ T cells and Th17/Th1 cell differentiation are critical events in psoriasis pathogenesis, but the associated molecular mechanism is still unclear. Here, using quantitative proteomics analysis we found that CDK7 expression was markedly increased in CD4+ T cells from psoriasis patients compared with healthy controls, and was positively correlated with psoriasis severity. Meanwhile, genetic or pharmacological inhibition of CDK7 ameliorated the severity of psoriasis in imiquimod-induced psoriasis-like mouse model and suppressed CD4+ T cell activation as well as Th17/Th1 cell differentiation in vivo and in vitro.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-15
      DOI: 10.1016/j.jid.2021.04.018
       
  • A targetable, non-canonical STAT3 activation induced by the tyrosine-less
           region of IL-22R orchestrates imiquimod-induced psoriasis-like dermatitis
           in mice

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      Authors: Camille Michiels; Léna Puigdevall, Perrine Cochez, Younes Achouri, Paméla Cheou, Emilie Hendrickx, Nicolas Dauguet, Christophe Blanchetot, Laure Dumoutier
      First page: 2668
      Abstract: Exacerbated IL-22 activity induces tissue inflammation and immune disorders such as psoriasis. However, because IL-22 is also essential for tissue repair and defense at barrier interfaces, targeting IL-22 activity to treat psoriasis bears the risk of deleterious effects at mucosal sites such as the gut. We previously showed, in vitro, that IL-22 signaling relies on IL-22Rα tyrosine–dependent and -independent pathways. The second depends on the C-terminal tyrosine-less region of IL-22Ra and leads to massive STAT3 activation.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-13
      DOI: 10.1016/j.jid.2021.04.016
       
  • TGF-β2 upregulates tyrosinase activity via Opsin3 in human skin
           melanocytes in vitro

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      Authors: Yu Wang; Yinghua Lan, Xincun Yang, Yangguang Gu, Hongguang Lu
      First page: 2679
      Abstract: Opsin3 (OPN3) is a potential key regulator of human melanocyte melanogenesis. How OPN3-mediated regulation of melanocyte melanogenesis is triggered is largely unclear. Transforming growth factor-β (TGF-β) can inhibit the growth of human melanocytes and reduce melanin synthesis in melanocytes. However, whether TGF-β2 can modulate pigmentation in normal human primary melanocytes via OPN3 is entirely unknown. Here, we constructed a co-culture model with human epidermal melanocytes and keratinocytes.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-21
      DOI: 10.1016/j.jid.2021.01.040
       
  • Inhibition of plasminogen activator inhibitor-1 blocks programmed death
           ligand 1 endocytosis and improves the response of melanoma cells to immune
           checkpoint blockade

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      Authors: Yu-Ju Tseng; Chih-Hung Lee, Wei-Yu Chen, Jenq-Lin Yang, Hong-Tai Tzeng
      First page: 2690
      Abstract: Immune checkpoint molecules especially programmed death 1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1) act as a major mechanism of cancer immune evasion. Although anti-PD-1/PD-L1 monotherapy increases therapeutic efficacy in melanoma treatment, only a subset of patients exhibits long-term tumor remission, and the underlying mechanism of resistance to PD-1/PD-L1 inhibitors remains unclear. In this study, we demonstrated that cell surface retention of PD-L1 inversely correlated with plasminogen activator inhibitor-1 (PAI-1) expression in vitro, in vivo and in clinical specimens.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-14
      DOI: 10.1016/j.jid.2021.03.030
       
  • Bestatin cream impairs solar simulated light-driven skin inflammation and
           skin carcinogenesis in mice

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      Authors: Simin Zhao; Ke Yao, Kangdong Liu, Limeng Huang, Yanan Jiang, Jian Li, Ziming Dong, Zigang Dong
      First page: 2699
      Abstract: Leukotriene A4 hydrolase (LTA4H) is an enzyme that catalyzes the production of the inflammatory mediator leukotriene B4 (LTB4), which is involved in inflammatory responses mediated through the LTB4/ LTB4 receptor type 1 (BLT1) signaling pathway. Here, we investigated whether bestatin, an LTA4H inhibitor, could suppress skin acute inflammation and carcinogenesis. In the clinic, BLT1 was significantly induced in human skin tissues after acute solar simulated light (SSL) exposure. BLT1 and NF-κB P65 expression were also increased in acute SSL induced mouse skin tissue.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-25
      DOI: 10.1016/j.jid.2021.03.032
       
  • Successful treatment of vitiligo with cold atmospheric plasma-activated
           hydrogel

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      Authors: Siyue Zhai; Meifeng Xu, Qiaosong Li, Kun Guo, Hailan Chen, Michael G. Kong, Yumin Xia
      First page: 2710
      Abstract: Vitiligo shows an insufficient response to current therapies, largely due to T lymphocyte dysfunction, abnormal inflammatory activation, and excessive oxidative stress in lesions. Cold atmospheric plasma (CAP) possesses pleiotropic anti-oxidant and anti-inflammatory properties and may offer an improvement to current treatment options. In this study, the efficacy and safety of CAP was investigated in a mouse model of vitiligo and a randomized and controlled trial of patients with active focal vitiligo.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-21
      DOI: 10.1016/j.jid.2021.04.019
       
  • Peroxiredoxin 4 improved aging-related delayed wound healing in mice

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      Authors: Reimon Yamaguchi; Xin Guo, Jianbo Zheng, Jing Zhang, Jia Han, Akihiro Shioya, Hidetaka Uramoto, Takashi Mochizuki, Sohsuke Yamada
      First page: 2720
      Abstract: Aging-related delayed wound healing is an issue of concern worldwide. Oxidative stress is involved in wound healing. Antioxidative enzymes have various roles in this process. Peroxiredoxin 4 (PRDX4), a member of the PRDX family, is upregulated after injury. To investigate the effects of PRDX4 on aging-related wound healing, we subjected C57BL/6J (wild-type [WT]), human PRDX4-transgenic (hPRDX4+/+), PRDX4-knockout (PRDX4-/y) mice of three age groups (young, adult and aged) to skin wound formation.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-21
      DOI: 10.1016/j.jid.2021.04.015
       
  • Adalimumab Induces a Wound Healing Profile in Patients with Hidradenitis
           Suppurativa by Regulating Macrophage Differentiation and Matrix
           Metalloproteinase Expression

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      Authors: Yonghao Cao; Bohdan P. Harvey, Feng Hong, Melanie Ruzek, Jing Wang, Erin R. Murphy, Zehra Kaymakcalan
      First page: 2730
      Abstract: Adalimumab (ADA) is the only FDA-approved treatment for moderate-to-severe hidradenitis suppurativa (HS), whereas etanercept (ETN) and certolizumab-pegol (CZP) have been shown to be ineffective, suggesting that the mechanism of action of ADA is distinct in HS and may contribute to improved wound healing. Given that macrophages (Mφ) play pivotal roles throughout the wound healing process, an in-vitro Mφ differentiation assay was carried out to assess the impact of TNF-anti-TNF complexes on these cells.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-06
      DOI: 10.1016/j.jid.2021.04.010
       
  • Unsuspected Associations with Variants within the Genes NOTCH4 and
           STEAP2-ASI Uncovered by a Genome-Wide Association Study in Endemic
           Pemphigus Foliaceus

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      Authors: Danillo G. Augusto; Rodrigo C. de Almeida, Ticiana D.J. Farias, Wagner C.S. Magalhães, Danielle Malheiros, Maria Fernanda Lima-Costa, Maurício L. Barreto, Bernardo L. Horta, Vinod Kumar, Michael Wittig, Andre Franke, Hauke Busch, Enno Schmidt, Ana Maria Roselino, Eduardo Tarazona-Santos, Angelica B.W. Boldt, Maria Luiza Petzl-Erler
      First page: 2741
      Abstract: Pemphigus foliaceus is a blistering autoimmune disease of the skin representing a public health issue, particularly in Brazil, where it is endemic and neglected. Sporadic cases are reported across the globe. Nevertheless, an astonishing prevalence of more than 3% was reported for endemic pemphigus foliaceus (EPF) in some Brazilian regions (Schmidt et al. 2019), the highest ever reported for an autoimmune disease worldwide. Although the reasons for its endemicity are not clear, it has been suggested that environmental factors such as agricultural activities, insect bites, and others may trigger the disease in genetically susceptible individuals (Aoki et al.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-12
      DOI: 10.1016/j.jid.2021.04.017
       
  • Infantile hemangioma and the risk factors in a Japanese population: A
           nationwide longitudinal study – The Japan Environment and Children’s
           Study (JECS)

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      Authors: Megumi Mizawa; Kenta Matsumura, Kei Hamazaki, Fumina Furukawa, Teruhiko Makino, Tadamichi Shimizu, Hidekuni Inadera, Japan Environment Children’s Study Group
      First page: 2745
      Abstract: Infantile hemangioma (IH) is the most common vascular tumor of infancy. We evaluated the incidence of and environmental risk factors for IH using data from the Japan Environment and Children's Study (JECS), a large-scale nationwide epidemiological study. The materials and methods are described in detail in the Supplementary Materials and Methods.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-06-08
      DOI: 10.1016/j.jid.2021.05.011
       
  • GWAS of 9,260 Japanese individuals identified IL4R and the MHC region as
           associated loci of total serum IgE levels

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      Authors: Kosuke Shido; Kaname Kojima, Matsuyuki Shirota, Kenshi Yamasaki, Ikuko N. Motoike, Atsushi Hozawa, Soichi Ogishima, Naoko Minegishi, Kozo Tanno, Fumiki Katsuoka, Gen Tamiya, Setsuya Aiba, Masayuki Yamamoto, Kengo Kinoshita
      First page: 2749
      Abstract: Immunoglobulin E (IgE) is an antibody produced by the immune system in response to helminth and parasites, and it has previously been found to be involved in eczema, ichthyosis and lupus, among other skin disorders(Bayry, 2016, Johansson et al., 2017, Kiritsi et al., 2015). According to twin and family studies, genetic factors affect total IgE levels, and their heritability was estimated as 36%-78% (Jacobsen et al., 2001, Meyers et al., 1987). Genome-wide association studies (GWASs) of total IgE levels in European populations (14,628 German individuals, 11,299 German individuals, and 8,539 Latino individuals) identified single-nucleotide polymorphisms (SNPs) nearby FCER1A, IL-13, STAT6, and ZNF365 (Granada et al., 2012, Moffatt et al., 2010, Pino-Yanes et al., 2015, Weidinger et al., 2008), while no significant loci other than the major histocompatibility complex (MHC) region was identified via GWASs in Asian populations (3,654 Japanese individuals, 877 Korean individuals, and 3,495 Chinese individuals) (Kim et al., 2013, Liao et al., 2013, Yatagai et al., 2013) (summarized in Table S2).
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-04-13
      DOI: 10.1016/j.jid.2021.02.762
       
  • Homozygous ITGA3 Missense Mutation in Adults in a Family with Syndromic
           Epidermolysis Bullosa (ILNEB)

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      Authors: Ágnes Kinyó; András László Kovács, Péter Degrell, Endre Kálmán, Nikoletta Nagy, Sarolta Kárpáti, Rolland Gyulai, Amir Hossein Saeidian, Leila Youssefian, Hassan Vahidnezhad, Jouni Uitto
      First page: 2752
      Abstract: Epidermolysis bullosa (EB), the prototype of skin fragility disorders, manifests with blistering and erosions of the skin and mucous membranes (Has et al., 2020) (Vahidnezhad et al., 2019a). The classic forms of EB are associated with 16 distinct genes expressed in the cutaneous basement membrane zone (Has et al., 2020). One such gene is ITGA3 encoding α3 integrin subunit, which combines with β1 subunit to form α3β1 integrin. Mutations in the ITGA3 gene have been reported in 10 cases with EB, and the characteristic feature in the majority of these patients is severe respiratory and renal involvement causing early postnatal demise (Has et al.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-05-20
      DOI: 10.1016/j.jid.2021.03.029
       
  • Frequent FGFR3 and Ras Gene Mutations in Skin Tags/Acrochordons

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      Authors: Satomi Aoki; Yoshiko Hirata, Tomoko Kawai, Kazuhiko Nakabayashi, Kenichiro Hata, Hisato Suzuki, Kenjiro Kosaki, Masayuki Amagai, Akiharu Kubo
      First page: 2756
      Abstract: The skin is subject to age-dependent development of benign tumors, the most common of which are seborrheic keratoses (SKs) and skin tags (STs). SKs are flat or dome-shaped nodules that develop predominantly on sun-exposed skin, while STs, also called acrochordons, are polypoid skin lesions that develop predominantly on the neck and axilla. Although polypoid or pedunculated protrusions sometimes develop from a part of SKs, SKs and STs are considered distinct tumors.
      Citation: Journal of Investigative Dermatology (2021)
      PubDate: 2021-04-29
      DOI: 10.1016/j.jid.2021.03.028
       
 
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