Subjects -> MEDICAL SCIENCES (Total: 8529 journals)
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DERMATOLOGY AND VENEREOLOGY (164 journals)                     

Showing 1 - 164 of 164 Journals sorted alphabetically
Acta Dermato-Venereologica     Open Access   (Followers: 12)
Acta Dermatovenerologica Croatica     Open Access   (Followers: 1)
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Advances in Dermatology     Full-text available via subscription   (Followers: 16)
Advances in Skin & Wound Care     Hybrid Journal   (Followers: 31)
African Journal of AIDS Research     Hybrid Journal   (Followers: 8)
AIDS     Hybrid Journal   (Followers: 23)
AIDS Care: Psychological and Socio-medical Aspects of AIDS/HIV     Hybrid Journal   (Followers: 9)
AIDS Patient Care and STDs     Hybrid Journal   (Followers: 3)
AIDS Research and Human Retroviruses     Hybrid Journal   (Followers: 9)
AIDS Research and Therapy     Open Access   (Followers: 15)
AIDS Research and Treatment     Open Access   (Followers: 2)
Aktuelle Dermatologie     Hybrid Journal   (Followers: 7)
Allergo Journal     Full-text available via subscription   (Followers: 2)
American Journal of Clinical Dermatology     Full-text available via subscription   (Followers: 26)
American Journal of Dermatopathology     Hybrid Journal   (Followers: 17)
Anais Brasileiros de Dermatologia     Open Access   (Followers: 2)
Anaplastology     Open Access  
Annales de Dermatologie et de Vénéréologie     Full-text available via subscription  
Archives de Pédiatrie     Full-text available via subscription  
Archives de sciences sociales des religions     Open Access   (Followers: 1)
Archives des Maladies du Coeur et des Vaisseaux - Pratique     Hybrid Journal  
Archives of Dermatological Research     Hybrid Journal   (Followers: 7)
Archives of Gerontology and Geriatrics     Hybrid Journal   (Followers: 13)
Archives of Industrial Hygiene and Toxicology     Open Access   (Followers: 8)
Archives of Medical Research     Hybrid Journal   (Followers: 3)
Archives of Physical Medicine and Rehabilitation     Hybrid Journal   (Followers: 55)
Archivio di Ortopedia e Reumatologia     Hybrid Journal  
Asian Journal of Dermatology     Open Access   (Followers: 2)
ästhetische dermatologie & kosmetologie     Full-text available via subscription  
Australasian Journal of Dermatology     Hybrid Journal   (Followers: 8)
Berkala Ilmu Kesehatan Kulit dan Kelamin / Periodical of Dermatology and Venereology     Open Access  
Biomedical Dermatology     Open Access  
BMC Dermatology     Open Access   (Followers: 13)
BMJ Sexual & Reproductive Health     Hybrid Journal   (Followers: 2)
British Journal of Dermatology     Hybrid Journal   (Followers: 54)
Case Reports in Dermatological Medicine     Open Access   (Followers: 2)
Case Reports in Dermatology     Open Access   (Followers: 10)
Clinical and Experimental Dermatology     Hybrid Journal   (Followers: 14)
Clinical Dermatology Review     Open Access   (Followers: 5)
Clinical Skin Cancer     Full-text available via subscription  
Clinical, Cosmetic and Investigational Dermatology     Open Access   (Followers: 10)
Clinics in Dermatology     Hybrid Journal   (Followers: 15)
Contact Dermatitis     Hybrid Journal   (Followers: 8)
Cosmetics     Open Access   (Followers: 5)
Current Dermatology Reports     Hybrid Journal   (Followers: 7)
Current Fungal Infection Reports     Hybrid Journal   (Followers: 5)
Current HIV Research     Hybrid Journal   (Followers: 7)
Current HIV/AIDS Reports     Hybrid Journal   (Followers: 6)
Current Sexual Health Reports     Hybrid Journal   (Followers: 3)
Cutaneous and Ocular Toxicology     Hybrid Journal   (Followers: 10)
Der Hautarzt     Hybrid Journal   (Followers: 2)
Dermatitis     Hybrid Journal   (Followers: 1)
Dermato-Endocrinology     Open Access   (Followers: 2)
Dermatología Venezolana     Open Access  
Dermatologic Clinics     Full-text available via subscription   (Followers: 4)
Dermatologic Reviews     Hybrid Journal  
Dermatologic Surgery     Hybrid Journal   (Followers: 8)
Dermatologic Therapy     Hybrid Journal   (Followers: 2)
Dermatologica Sinica     Open Access  
Dermatological Nursing     Full-text available via subscription   (Followers: 2)
Dermatology     Full-text available via subscription   (Followers: 20)
Dermatology and Cosmetic     Open Access   (Followers: 8)
Dermatology and Therapy     Open Access   (Followers: 4)
Dermatology Online Journal     Open Access   (Followers: 1)
Dermatology Reports     Open Access   (Followers: 3)
Dermatology Research and Practice     Open Access   (Followers: 4)
Dermatology Times     Free  
Dermatopathology     Open Access   (Followers: 3)
Egyptian Journal of Dermatology and Venerology     Open Access   (Followers: 1)
EMC - Cosmetologia Medica e Medicina degli Inestetismi Cutanei     Full-text available via subscription  
EMC - Dermatología     Full-text available via subscription   (Followers: 1)
European Journal of Dermatology     Hybrid Journal   (Followers: 15)
Experimental Dermatology     Hybrid Journal   (Followers: 10)
Expert Review of Dermatology     Hybrid Journal   (Followers: 14)
Forum Dermatologicum     Hybrid Journal  
Graefe's Archive for Clinical and Experimental Ophthalmology     Hybrid Journal   (Followers: 8)
Güncel Dermatoloji Dergisi     Open Access  
HautinForm     Full-text available via subscription  
hautnah     Hybrid Journal  
hautnah dermatologie     Hybrid Journal  
HIV & AIDS Review     Full-text available via subscription   (Followers: 13)
HIV Clinical Trials     Hybrid Journal   (Followers: 5)
HIV Medicine     Hybrid Journal   (Followers: 3)
Indian Dermatology Online Journal     Open Access   (Followers: 3)
Indian Journal of Dermatology     Open Access   (Followers: 2)
Indian Journal of Dermatology, Venereology and Leprology     Open Access   (Followers: 4)
Indian Journal of Dermatopathology and Diagnostic Dermatology     Open Access  
Indian Journal of Drugs in Dermatology     Open Access   (Followers: 1)
Indian Journal of Paediatric Dermatology     Open Access   (Followers: 2)
Indian Journal of Sexually Transmitted Diseases and AIDS     Open Access   (Followers: 2)
International Archives of Medicine     Open Access   (Followers: 3)
International Journal of Dermatology     Hybrid Journal   (Followers: 15)
International Journal of Dermatology and Clinical Research     Open Access   (Followers: 2)
International Journal of Research in Dermatology     Open Access   (Followers: 1)
International Journal of STD & AIDS     Hybrid Journal   (Followers: 7)
International Journal of Women's Dermatology     Open Access   (Followers: 1)
International STD Research & Reviews     Open Access   (Followers: 1)
JAAD Case Reports     Open Access   (Followers: 1)
JAIDS : Journal of Acquired Immune Deficiency Syndromes     Hybrid Journal   (Followers: 4)
JAMA Dermatology     Full-text available via subscription   (Followers: 49)
JAMA Facial Plastic Surgery     Full-text available via subscription   (Followers: 12)
JMIR Dermatology     Open Access   (Followers: 1)
Journal of AIDS & Clinical Research     Open Access   (Followers: 3)
Journal of Clinical & Experimental Dermatology Research     Open Access   (Followers: 6)
Journal of Clinical and Investigative Dermatology     Open Access   (Followers: 2)
Journal of Cosmetic Dermatology     Hybrid Journal   (Followers: 10)
Journal of Cosmetics, Dermatological Sciences and Applications     Open Access   (Followers: 7)
Journal of Cutaneous Immunology and Allergy     Open Access  
Journal of Cutaneous Medicine and Surgery     Full-text available via subscription  
Journal of Dermatological Research     Open Access  
Journal of Dermatological Science     Hybrid Journal   (Followers: 2)
Journal of Dermatological Science Supplement     Full-text available via subscription   (Followers: 1)
Journal of Dermatological Treatment     Hybrid Journal   (Followers: 2)
Journal of Dermatology & Dermatologic Surgery     Open Access   (Followers: 1)
Journal of General-Procedural Dermatology & Venereology Indonesia     Open Access  
Journal of HIV/AIDS & Social Services     Hybrid Journal   (Followers: 9)
Journal of Investigative Dermatology     Hybrid Journal   (Followers: 28)
Journal of Investigative Dermatology Symposium Proceedings     Full-text available via subscription  
Journal of Sexual Medicine     Hybrid Journal   (Followers: 6)
Journal of Sexually Transmitted Diseases     Open Access   (Followers: 3)
Journal of Skin and Stem Cell     Open Access   (Followers: 3)
Journal of Skin Cancer     Open Access   (Followers: 3)
Journal of Surgical Dermatology     Open Access   (Followers: 1)
Journal of the American Academy of Dermatology     Full-text available via subscription   (Followers: 37)
Journal of the Dermatology Nurses' Association     Hybrid Journal   (Followers: 3)
Journal of the Egyptian Women’s Dermatologic Society     Partially Free  
Journal of the European Academy of Dermatology and Venereology     Hybrid Journal   (Followers: 15)
Journal of the International AIDS Society     Open Access   (Followers: 10)
Journal of the Saudi Society of Dermatology & Dermatologic Surgery     Open Access   (Followers: 1)
Karger Kompass Dermatologie     Full-text available via subscription  
Karger Kompass Pneumologie     Full-text available via subscription   (Followers: 1)
Langenbeck's Archives of Surgery     Hybrid Journal   (Followers: 4)
Medical and Surgical Dermatology     Hybrid Journal   (Followers: 1)
Medical Mycology     Open Access   (Followers: 4)
Nepal Journal of Dermatology, Venereology & Leprology     Open Access   (Followers: 1)
Neurobehavioral HIV Medicine     Open Access   (Followers: 2)
OA Dermatology     Open Access   (Followers: 1)
Open AIDS Journal     Open Access  
Open Dermatology Journal     Open Access  
Perspectives On Sexual and Reproductive Health     Hybrid Journal   (Followers: 7)
Pigment International     Open Access   (Followers: 1)
Psoriasis : Targets and Therapy     Open Access   (Followers: 4)
Revista Internacional de Ciencias Podológicas     Open Access  
SAHARA : Journal of Social Aspects of HIV / AIDS Research Alliance     Open Access   (Followers: 5)
Scars, Burns & Healing     Open Access  
Serbian Journal of Dermatology and Venereology     Open Access   (Followers: 1)
Sex Education: Sexuality, Society and Learning     Hybrid Journal   (Followers: 5)
Sexual & Reproductive Healthcare     Hybrid Journal   (Followers: 2)
Sexual Health     Hybrid Journal   (Followers: 4)
Sexually Transmitted Diseases     Hybrid Journal   (Followers: 6)
Sexually Transmitted Infections     Hybrid Journal   (Followers: 6)
Skin Appendage Disorders     Full-text available via subscription   (Followers: 1)
Skin Pharmacology and Physiology     Full-text available via subscription   (Followers: 7)
Skin Research and Technology     Hybrid Journal   (Followers: 7)
Southern African Journal of HIV Medicine     Open Access   (Followers: 3)
Sri Lanka Journal of Sexual Health and HIV Medicine     Open Access  
Studies in Gender and Sexuality     Hybrid Journal   (Followers: 21)
Surgical & Cosmetic Dermatology     Open Access   (Followers: 3)
The Journal of Dermatology     Hybrid Journal   (Followers: 5)
The Rose Sheet     Full-text available via subscription   (Followers: 2)
Vestnik dermatologii i venerologii     Open Access  
Veterinary Dermatology     Hybrid Journal   (Followers: 8)


Similar Journals
Journal Cover
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  [3204 journals]
  • SnapshotDx Quiz: April 2020
    • Authors: Jeffrey D. McBride; Mariya Miteva
      Abstract: Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Snapshot Dx 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 the JID article by Pogatzki-Zahn et al. (2020) (
      Citation: Journal of Investigative Dermatology 140, 4 (2020)
      PubDate: 2020-04
      DOI: 10.1016/j.jid.2020.02.008
      Issue No: Vol. 140, No. 4 (2020)
  • Subscription Information
    • Citation: Journal of Investigative Dermatology 140, 4 (2020)
      PubDate: 2020-04
      DOI: 10.1016/S0022-202X(20)30172-X
      Issue No: Vol. 140, No. 4 (2020)
  • Cells to Surgery Quiz: April 2020
    • Authors: Pooja Gurnani; Natalie M. Williams, Jun Long, John Zade, Ali Rajabi-Estarabadi, Keyvan Nouri
      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 the JID article by Liu et al. (
      Citation: Journal of Investigative Dermatology 140, 4 (2020)
      PubDate: 2020-04
      DOI: 10.1016/j.jid.2020.02.007
      Issue No: Vol. 140, No. 4 (2020)
  • Clinical Snippets
    • First page: 721
      Abstract: Urticaria is a common feature that results from multiple etiologies, including NLRP3-associated autoinflammatory disease. Assrawi et al. identified two distinct mosaic mutations in the key inflammasome protein NLRP3 in two unrelated elderly patients with late-onset chronic urticaria accompanied by systemic inflammation. These gain-of-function mutations resulted in increased inflammasome activation and secretion of IL-1β, and treatment of these patients with the IL-1β antagonist anakinra resulted in complete remission of symptoms.
      Citation: Journal of Investigative Dermatology 140, 4 (2020)
      PubDate: 2020-04
      DOI: 10.1016/j.jid.2020.02.001
      Issue No: Vol. 140, No. 4 (2020)
  • Editors’ Picks
    • First page: 722
      Abstract: Mistry et al. examined the transcription, epigenetic, and functional characteristics of low-density granulocytes (LPGs), proinflammatory neutrophils that are more frequent in patients with systemic lupus erythematosus (SLE) and that have been implicated in endothelial damage and vascular dysfunction. Two distinct populations of LPGs were identified in patients with SLE based on expression of CD10. A small subset of CD10– LPGs displays a more immature neutrophil type and exhibits upregulation of genes associated with neutrophil precursors and downregulation of immune response genes.
      Citation: Journal of Investigative Dermatology 140, 4 (2020)
      PubDate: 2020-04
      DOI: 10.1016/j.jid.2020.02.002
      Issue No: Vol. 140, No. 4 (2020)
  • Research Techniques Made Simple: CRISPR Genetic Screens
    • Authors: Auke B.C. Otten; Bryan K. Sun
      Pages: 723 - 728.e1
      Abstract: CRISPR and Cas proteins, often referred to as CRISPR/Cas, are the components of a bacterial genome editing system that can be used to perturb genes in cells and tissues. A classic application is to use CRISPR/Cas to generate genetic loss-of-function. When performed at large scale and combined with deep sequencing techniques, CRISPR-based perturbations can be performed in a high throughput setting to screen many candidate genomic elements for their roles in a phenotype of interest. Here, we discuss major considerations in the design, execution, and analysis of CRISPR screens.
      Citation: Journal of Investigative Dermatology 140, 4 (2020)
      PubDate: 2020-04
      DOI: 10.1016/j.jid.2020.01.018
      Issue No: Vol. 140, No. 4 (2020)
  • Recent Advances in Understanding Pemphigus and Bullous Pemphigoid
    • Authors: Christoph M. Hammers; John R. Stanley
      Pages: 733 - 741
      Abstract: For many years, The Journal of Investigative Dermatology (JID) has been a leader in our understanding of many aspects of the major autoimmune blistering skin diseases, pemphigus and bullous pemphigoid. The purpose of this review is to highlight and summarize those advances by discussing the respective articles, published in the JID from 2015 to 2019. Seminal articles from elsewhere in the literature that set the stage for those advances, or that are “classics” in the area, are also included to provide context and a more complete picture.
      Citation: Journal of Investigative Dermatology 140, 4 (2020)
      PubDate: 2020-04
      DOI: 10.1016/j.jid.2019.11.005
      Issue No: Vol. 140, No. 4 (2020)
  • Kallikrein-6–Regulated Pathways Shed Light on New Potential Targets in
           Varicella Zoster Virus Infection
    • Authors: Stephan M. Caucheteux; Vincent Piguet
      Pages: 741 - 742
      Abstract: Varicella zoster virus, the worldwide infectious human virus responsible for acute varicella and chickenpox, commonly spreads from exposure through contact with a skin lesion or airborne respiratory droplets. Keratinocytes, major targets and source of transmission of the virus present in the skin, represent an ideal choice of cell to stop early virus progression. In their recent study, Tommasi et al. show regulatory mechanisms of cytokeratin 10 through the protease kallikrein-6 as a suitable and druggable pathway to reduce varicella zoster virus dissemination.
      Citation: Journal of Investigative Dermatology 140, 4 (2020)
      PubDate: 2020-04
      DOI: 10.1016/j.jid.2019.11.006
      Issue No: Vol. 140, No. 4 (2020)
  • Cellular Phenotypic Plasticity of Cutaneous Melanoma: A Complex Puzzle
    • Authors: Sandeep S. Joshi; Thomas J. Hornyak
      Pages: 743 - 745
      Abstract: Wenzina et al. (2020) explore the potential role of E-cadherin (CDH1) as a marker for invasive behavior in melanoma. The authors show that CDH1 expression is modulated by p38 signaling, and that manipulation of this pathway can impede endothelial disruption and lung dissemination in vivo and in vitro. The downstream markers PODXL and DEL of the invasive phenotype are associated with a poor prognosis.
      Citation: Journal of Investigative Dermatology 140, 4 (2020)
      PubDate: 2020-04
      DOI: 10.1016/j.jid.2019.11.025
      Issue No: Vol. 140, No. 4 (2020)
  • Innate Cancer Immunoediting
    • Authors: Tobias Bald; Mark J. Smyth
      Pages: 745 - 747
      Abstract: Immune cells detect and destroy cancer cells; however, very early changes in cancer genome and phenotype coupled with immune system selection cause escape variant survival in a process called cancer immunoediting. Although adaptive immunity is important for this process, the report by Kubick et al. provides novel insights into the role of innate immune cells for immunoediting of early transformed epithelial cells.
      Citation: Journal of Investigative Dermatology 140, 4 (2020)
      PubDate: 2020-04
      DOI: 10.1016/j.jid.2019.09.015
      Issue No: Vol. 140, No. 4 (2020)
  • Theranostic Advances in Vascular Malformations
    • Authors: Valérie Dekeuleneer; Emmanuel Seront, An Van Damme, Laurence M. Boon, Miikka Vikkula
      Pages: 756 - 763
      Abstract: Vascular malformations are subdivided into capillary, lymphatic, venous, arteriovenous, and mixed malformations, according to the type of affected vessels. Until a few years ago, treatment options were limited to sclerotherapy and/or surgery. Since, it has been demonstrated that the majority of vascular malformations are caused by inherited or somatic mutations in various genes. These mutations lead to hyperactivity of two major signaling pathways: the RAS/mitogen-activated protein kinase and the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways.
      Citation: Journal of Investigative Dermatology 140, 4 (2020)
      PubDate: 2020-04
      Issue No: Vol. 140, No. 4 (2020)
  • Artificial Intelligence in Dermatology: A Primer
    • Authors: Albert T. Young; Mulin Xiong, Jacob Pfau, Michael J. Keiser, Maria L. Wei
      Abstract: Artificial intelligence (AI) is becoming increasingly important in dermatology, with studies reporting accuracy matching or exceeding dermatologists for the diagnosis of skin lesions from clinical and dermoscopic images. However, real-world clinical validation is currently lacking. We review dermatological applications of deep learning, the leading AI technology for image analysis, and discuss its current capabilities, potential failure modes, and challenges surrounding performance assessment and interpretability.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-27
      DOI: 10.1016/j.jid.2020.02.026
    • Authors: Andrea N. Naranjo; Geethani Bandara, Yun Bai, Margery G. Smelkinson, Araceli Tobío, Hirsh D. Komarow, Steven E. Boyden, Daniel L. Kastner, Dean D. Metcalfe, Ana Olivera
      Abstract: A role for the adhesion G-protein coupled receptor ADGRE2 (EMR2) in mechanosensing was revealed by the finding of a missense substitution (p.C492Y) associated with familial vibratory urticaria (VU). In these patients, friction of the skin induces mast cell hyper-degranulation through p.C492Y-ADGRE2, causing localized hives, flushing and hypotension. We have now characterized the responses and intracellular signals elicited by mechanical activation in human mast cells expressing p.C492Y-ADGRE2 and attached to dermatan sulfate, a ligand for ADGRE2.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-25
      DOI: 10.1016/j.jid.2020.03.936
  • Rosacea is Characterized by a Profoundly Diminished Skin Barrier
    • Authors: Barbara Medgyesi; Zsolt Dajnoki, Gabriella Béke, Krisztián Gáspár, Imre Lőrinc Szabó, Eszter Anna Janka, Szilárd Póliska, Zoltán Hendrik, Gábor Méhes, Dániel Törőcsik, Tamás Bíró, Anikó Kapitány, Andrea Szegedi
      Abstract: Rosacea is a common, chronic inflammation of sebaceous gland-rich facial skin characterized by severe skin dryness, elevated pH, transepidermal water loss, and decreased hydration levels. Until now, there has been no thorough molecular analysis of permeability barrier alterations in the skin of rosacea patients. Thus, we aimed to investigate the barrier alterations in papulopustular rosacea (PPR) samples compared to healthy sebaceous gland-rich (SGR) skin, using RNASeq analysis (n=8). Pathway analyses by Cytoscape ClueGo revealed 15 significantly enriched pathways related to skin barrier formation.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-19
      DOI: 10.1016/j.jid.2020.02.025
  • Skin infiltration of pathogenic migratory and resident T cells is
           decreased by Secukinumab treatment in psoriasis
    • Authors: Toshiharu Fujiyama; Takatsune Umayahara, Kazuo Kurihara, Takatoshi Shimauchi, Taisuke Ito, Masahiro Aoshima, Emiko Otobe, Hideo Hashizume, Hiroaki Yagi, Yoshiki Tokura
      Abstract: To the editor
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-18
      DOI: 10.1016/j.jid.2020.02.024
  • Epidermal Mineralocorticoid Receptor inactivation affects the homeostasis
           of all skin layers in chronologically aged mice
    • Authors: Judit Bigas; Lisa M. Sevilla, Paloma Pérez
      Abstract: The endogenous increased production of glucocorticoids (GCs) in the skin of the elderly population contributes to age-related defects strikingly similar to those occurring after pharmacological treatments with GCs.GCs act through the ligand-dependent transcription factors GC receptor (GR) and mineralocorticoid receptor (MR). We demonstrated that epidermal MR plays non-redundant roles relative to GR in adult mouse skin homeostasis; however, its relative contribution to natural skin aging has not been previously investigated.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-18
      DOI: 10.1016/j.jid.2020.03.933
  • Meeting Report of the 16th International Langerhans Cell Workshop: Recent
           developments in Langerhans cell and skin dendritic cell biology and their
           therapeutic application
    • Authors: Björn E. Clausen; Nikolaus Romani, Patrizia Stoitzner
      Abstract: The 16th International Workshop on Langerhans Cells was organized by Björn E. Clausen, with the help of Patrizia Stoitzner and Nikolaus Romani in Budenheim near Mainz, Germany. From October 3rd through 6th, 2019, more than 100 scientists from all over the world presented their cutting-edge work and technological advances in the field of skin immunity with a special focus on Langerhans cells (LC) and dermal dendritic cells (DC). Novel insights into the development and homeostasis of LC and dermal DC and their respective functional roles in health and disease were discussed.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-18
      DOI: 10.1016/j.jid.2020.02.022
  • Pivotal involvement of the CX3CL1-CX3CR1 axis for the recruitment of M2
           tumor-associated macrophages in skin carcinogenesis
    • Authors: Yuko Ishida; Yumi Kuninaka, Yuki Yamamoto, Mizuho Nosaka, Akihiko Kimura, Fukumi Furukawa, Naofumi Mukaida, Toshikazu Kondo
      Abstract: We previously revealed the crucial roles of a chemokine, CX3CL1, and its receptor, CX3CR1, in skin wound healing. Although repeated wounds frequently develop into skin cancer, the roles of CX3CL1 in skin carcinogenesis remain elusive. Here, we proved that CX3CL1 protein expression and CX3CR1+ macrophages were observed in human skin cancer tissues. Similarly, we observed the enhancement of CX3CL1 expression and the abundant accumulation of CX3CR1+ tumor-associated macrophages (TAMs) with M2-like phenotypes in the skin carcinogenesis process induced by the combined treatment with 7,12-dimethylbenz-(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-13
      DOI: 10.1016/j.jid.2020.02.023
  • Prognostic impact of perineural invasion in cutaneous squamous cell
           carcinoma. Results of a prospective study of 1399 tumors
    • Authors: Konrad Haug; Helmut Breuninger, Gisela Metzler, Thomas Eigentler, Martin Eichner, Hans-Martin Häfner, Saskia M. Schnabl
      Abstract: Perineural infiltration (PNI) and desmoplasia are believed to be high-risk factors in the prognosis of squamous-cell-carcinoma (SCC). In the literature, dependences between PNI, de-differentiation, and desmoplasia remain unclear. The aim of this study was to analyze the respective prognostic impact of these factors in regard to local recurrence and metastasis.Between 2005 and 2015, 1399 unselected primary SCCs of 1434 patients were diagnosed. If a patient had multiple tumours, the tumour with the highest risk profile was selected.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-10
      DOI: 10.1016/j.jid.2020.01.035
  • Transgenic kallikrein 14 mice display major hair shaft defects associated
           with desmoglein 3 and 4 degradation, abnormal epidermal differentiation
           and Il-36 signature
    • Authors: Olivier Gouin; Claire Barbieux, Florent Leturcq, Mathilde Bonnet des Claustres, Evgeniya Petrova, Alain Hovnanian
      Abstract: Netherthon syndrome (NS) is a rare autosomal recessive skin disease caused by loss-of-function mutations in SPINK5 encoding Lymphoepithelial Kazal-Type-related Inhibitor (LEKTI) that results in unopposed activity of epidermal kallikrein-related peptidases (KLKs), mainly KLK5, KLK7 and KLK14. While the function of KLK5 and KLK7 has been previously studied, the role of KLK14 in skin homeostasis and its contribution to NS pathogenesis remain unknown. We generated a transgenic murine model overexpressing human KLK14 (TghKLK14) in stratum granulosum.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-10
  • Mutation signatures in melanocytic nevi reveal characteristics of
           defective DNA repair
    • Authors: Mitchell S. Stark; Evgeniya Denisova, Trent A. Kays, Barbara Heidenreich, Sivaramakrishna Rachakonda, Celia Requena, Richard A. Sturm, H. Peter Soyer, Eduardo Nagore, Rajiv Kumar
      Abstract: Nevi are common benign melanocytic neoplasms that can be found on any skin location and share many of the genomic hallmarks of melanoma. It is well known that BRAF is frequently mutated in nevi (Pollock et al., 2003) and it has been confirmed, that in a mutually exclusive relationship, BRAF or NRAS are mutated in 100% of common acquired nevi (Kumar et al., 2004, Tan et al., 2018). In our recent report involving whole-exome sequencing of acquired nevi (Stark et al., 2018), ultra-violet radiation (UVR) related somatic mutation signatures (“signature 7”) (Alexandrov et al., 2013) were frequently observed in all lesions that were located on sun-exposed sites.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-06
      DOI: 10.1016/j.jid.2020.02.021
  • Optical Coherence Tomography for non-invasive diagnosis and subtyping of
           Basal Cell Carcinoma, a prospective cohort study.
    • Authors: K.A.E. Sinx; Loo E. van, E.H.J. Tonk, N.W.J. Kelleners-Smeets, V.J.L. Winnepenninckx, P.J. Nelemans, K. Mosterd
      Abstract: Non-invasive diagnostic strategies, such as optical coherence tomography (OCT) enable detailed examination of skin tissue architecture and have potential for identification and subtyping of BCC.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-05
      DOI: 10.1016/j.jid.2020.01.034
  • Divergent Roles of Epithelium-Derived Alarmins in Notch Signaling
           Deficient Skin
    • Authors: Jonathan L. Messerschmidt; Kaitlin E. Dempsey, Kayla S. Dillon, Shadmehr Demehri
      Abstract: Epithelium-derived alarmin cytokines, thymic stromal lymphopoietin (TSLP), Interleukin (IL)-33, and IL-25, polarize T cells toward the TH2 phenotype at barrier sites to fight pathogens and allergens (Hammad and Lambrecht, 2015). TH2 cells are increasingly recognized as key players in barrier repair to prevent tissue damage following environmental insults like parasite infection (Chen et al., 2012). Furthermore, TSLP-induced TH2 cell immunity is critical for suppressing epithelial tumor development in mice (Demehri et al., 2016, Demehri et al., 2012) and humans (Cunningham et al., 2017).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-05
      DOI: 10.1016/j.jid.2020.02.020
  • Recurrent oncogenic JAK and STAT alterations in cutaneous CD30-positive
           lymphoproliferative disorders
    • Authors: Katja Maurus; Silke Appenzeller, Sabine Roth, Stephanie Brändlein, Hermann Kneitz, Matthias Goebeler, Andreas Rosenwald, Eva Geissinger, Marion Wobser
      Abstract: The group of cutaneous CD30-positive lymphoproliferative disorders (LPD) comprises two different entities, namely lymphomatoid papulosis (LyP) and cutaneous anaplastic large T-cell lymphoma (cALCL). LyP constitutes a benign lymphoproliferation with spontaneously regressing papules, whereas cALCL presents with solitary or multiple skin tumors with a low propensity to disseminate.To elucidate the hitherto largely unknown molecular pathogenesis of these entities, we performed comprehensive next generation sequencing in a well-characterized cohort of 12 patients.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-05
      DOI: 10.1016/j.jid.2020.02.019
  • The role of teledermatology and teledermoscopy in the diagnosis of actinic
           keratosis and field cancerization
    • Authors: J. Sola-Ortigosa; C. Muñoz-Santos, T. Masat-Ticó, J. Isidro-Ortega, A. Guilabert, Grup d’Estudi de Teledermatologia del Vallès Oriental
      Abstract: Actinic keratosis (AK) and field cancerization are increasing health problems insufficiently diagnosed by primary care physicians (PCP). The objective was to assess the validity and reliability of teledermatology (TD) and teledermoscopy (TDS) in the diagnosis of AK and field cancerization in a gatekeeper healthcare model. A prospective diagnostic test evaluation was done to assess the diagnostic concordance, accuracy and performance parameters and inter/intraobserver concordances of TD and TDS compared with dermatologists’ face-to-face evaluation or histopathology.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-03
      DOI: 10.1016/j.jid.2020.02.013
  • Low prevalence of gamma-secretase complex gene mutations in a large cohort
           of predominantly Caucasian patients with Hidradenitis Suppurativa
    • Authors: Sabine Duchatelet; Snaigune Miskinyte, Maia Delage, Marie-Noëlle Ungeheuer, Thi Lam, Farida Benhadou, Véronique Del Marmol, Allard R.J. V. Vossen, Errol P. Prens, Olivier Cogrel, Marie Beylot-Barry, Céline Girard, Julien Vidil, Olivier Join-Lambert, Mélanie Parisot, Patrick Nitschké, Sylvain Hanein, Sylvie Fraitag, Hessel H. Van der Zee, Didier Bessis, Giovanni Damiani, Andrea Altomare, Yi-Hua Liao, Georgios Nikolakis, Christos C. Zouboulis, Aude Nassif, Alain Hovnanian
      Abstract: Hidradenitis suppurativa (HS) is a chronic dermatosis characterized by nodules and abscesses in apocrine gland-bearing sites. Mutations in three gamma-secretase complex (GSC) genes have been identified in autosomal dominant forms of HS (Frew et al., 2017) (Tables S1-S2). NCSTN, PSEN1 and PSENEN mutations have been reported in 41 unrelated HS patients, one Chinese HS family and 21 unrelated HS patients with or without Dowling-Degos disease (DDD) respectively (Frew et al., 2017). The functional consequences of these mutations are yet to be elucidated.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-03
  • Predictable CRISPR/Cas9-Mediated COL7A1 Reframing for Dystrophic
           Epidermolysis Bullosa
    • Authors: Thomas Kocher; Oliver Patrick March, Johannes Bischof, Bernadette Liemberger, Stefan Hainzl, Alfred Klausegger, Anna Hoog, Dirk Strunk, Johann Wolfgang Bauer, Ulrich Koller
      Abstract: End joining-based gene editing is frequently used for efficient reframing and knock-out of target genes. However, the associated random, unpredictable and often heterogeneous repair outcomes limit its applicability for therapeutic approaches. Recent studies revealed more precise and predictable outcomes simply based upon the sequence context at the CRISPR/Cas9 target site. The severe dystrophic form of the blistering skin disease epidermolysis bullosa (DEB) represents a suitable model platform to test these recent developments for the disruption and reframing of dominant and recessive alleles, respectively, both frequent in DEB.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-03
      DOI: 10.1016/j.jid.2020.02.012
  • GPR119 is a potent regulator of human sebocyte biology
    • Authors: Arnold Markovics; Ágnes Angyal, Kinga Fanni Tóth, Dorottya Ádám, Zsófia Pénzes, József Magi, Ágnes Pór, Ilona Kovács, Dániel Törőcsik, Christos C. Zouboulis, Tamás Bíró, Attila Oláh
      Abstract: We have previously shown that endocannabinoids promote sebaceous lipogenesis, and sebocytes are involved in the metabolism of the “endocannabinoid-like” substance oleoylethanolamide (OEA). OEA is an endogenous activator of GPR119, a recently de-orphanized receptor, which is currently being investigated as a promising anti-diabetic drug target. Thus, in the current study, we investigated the effects of OEA as well as the expression and role of GPR119 in human sebocytes.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-03
      DOI: 10.1016/j.jid.2020.02.011
  • Inhibition of endoglin exerts anti-tumor effects through the regulation of
           non-Smad TGF-β signaling in angiosarcoma
    • Authors: Ryoko Sakamoto; Ikko Kajihara, Hitomi Miyauchi, Saki Maeda-Otsuka, Saori Yamada-Kanazawa, Soichiro Sawamura, Hisashi Kanemaru, Katsunari Makino, Jun Aoi, Takamitsu Makino, Satoshi Fukushima, Mamiko Masuzawa, Mikio Masuzawa, Yasuyuki Amoh, Daichi Hoshina, Riichiro Abe, Hironobu Ihn
      Abstract: Angiosarcoma is a rare malignant tumor derived from endothelial cells, and its prognosis is poor because advanced angiosarcoma is often resistant to taxane therapy. Endoglin (CD105) acts as a coreceptor for transforming growth factor-β (TGF-β) signaling, and is overexpressed in tumor-associated endothelial cells and enhances tumor angiogenesis. Numerous clinical trials are testing the effectiveness of anti-endoglin antibodies in various types of malignancies. Here, we investigated the role of endoglin in the pathogenesis of angiosarcoma and whether endoglin inhibition results in anti-tumor activity.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-03
      DOI: 10.1016/j.jid.2020.01.031
  • Pemphigus vulgaris and foliaceus IgG autoantibodies directly block
           heterophilic trans-interaction between desmoglein and desmocollin
    • Authors: Ken Ishii; Kenji Yoshida, John R. Stanley, Jun Yamagami, Masayuki Amagai, Akira Ishiko
      Abstract: Anti-desmoglein (Dsg) 1 and Dsg3 IgG autoantibodies in pemphigus foliaceus (PF) and vulgaris (PV) cause blisters through loss of desmosomal adhesion. It is controversial whether blister formation is due to direct inhibition of Dsg or intracellular signaling events causing desmosome destabilization or both. Recent studies show that heterophilic binding between Dsg and desmocollin (Dsc) is the fundamental adhesive unit of desmosomes. To eliminate cellular contributions to potential pathogenicity of pemphigus Abs, bead assays coated with recombinant Dsg1, Dsc1, Dsg3, or Dsc3 ectodomains were developed.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-03
      DOI: 10.1016/j.jid.2020.02.010
  • BRD4 is necessary for differentiation downstream of epidermal lineage
           determining transcription factors
    • Authors: Jackson Jones; Yifang Chen, Manisha Tiwari, Jingting Li, Ji Ling, George L. Sen
      Abstract: The human epidermis is a stratified epithelial tissue that protects the body from the outside environment. The integrity of this tissue relies on the balance of self-renewal and differentiation of the stem and progenitor keratinocyte population of the basal layer (Ge and Fuchs, 2018). Issues affecting various aspects of the differentiation program can result in a compromised skin barrier. A compromised barrier can lead to diseases such as ichthyosis, atopic dermatitis, and psoriasis which can impact up to 20% of the population (Lopez-Pajares et al., 2013).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-03
      DOI: 10.1016/j.jid.2020.01.030
  • TEAD1 and TEAD3 play redundant roles in the regulation of human epidermal
    • Authors: Jingting Li; Manisha Tiwari, Xiaojun Xu, Yifang Chen, Pablo Tamayo, George L. Sen
      Abstract: The evolutionary and functionally conserved Hippo signaling pathway is essential for the regulation of cell growth, proliferation, and organ development (Moya and Halder, 2019). Activation of the Hippo pathway leads to phosphorylation and inactivation of the transcriptional co-activator and major effector Yes-associated protein 1 (YAP1). Upon turning off the Hippo pathway, YAP is dephosphorylated which allows translocation to the nucleus to act as a co-activator with the TEAD family of transcription factors to drive the expression of genes essential for cell growth and proliferation.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-03
      DOI: 10.1016/j.jid.2020.01.029
  • Enhanced and sustained cutaneous delivery of vismodegib by ablative
           fractional laser and microemulsion formulation
    • Authors: Uffe Høgh Olesen; Gael Clergeaud, Kristoffer Kjærgaard Hendel, Kelvin Yeung, Catharina Margrethe Lerche, Thomas Lars Andresen, Merete Haedersdal
      Abstract: Oral administration of vismodegib for basal cell carcinoma treatment is limited by significant class-specific systemic side-effects. We investigated the approach of combining ablative fractional laser (AFL)-assisted drug delivery with an extended-release microemulsion formulation of vismodegib to provide efficient cutaneous delivery in vivo.The developed formulation consisted of an oil-in-water (o/w) microemulsion stabilized by tween-80. Pig skin was exposed to AFL followed by topical application of vismodegib microemulsion for 4 hours.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-03-02
      DOI: 10.1016/j.jid.2020.01.032
  • The polyamine putrescine promotes human epidermal melanogenesis
    • Authors: Aishwarya Sridharan; Meng Shi, Vonny Ivon Leo, Nagavidya Subramaniam, Thiam Chye Lim, Takeshi Uemura, Kazuei Igarashi, Steven Thng Tien Guan, Nguan Soon Tan, Leah A. Vardy
      Abstract: Hyper-pigmentary conditions can arise when melanogenesis in the epidermis is mis-regulated. Understanding the pathways underlying melanogenesis is essential for the development of effective treatments. Here, we show that a group of metabolites called polyamines are important in the control of melanogenesis in human skin. Polyamines are cationic molecules present in all cells and are essential for cellular function. We show that polyamine regulator ODC1 is upregulated in melanocytes from melasma lesional skin.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-28
      DOI: 10.1016/j.jid.2020.02.009
  • Involvement of p53 acetylation in growth suppression of Cutaneous T-cell
           lymphomas induced by HDAC inhibition
    • Authors: Xiaoxuan Yu; Hui Li, Mengyuan Zhu, Po Hu, Xiao Liu, Yingjie Qing, Xiangyuan Wang, Hongzheng Wang, Zhanyu Wang, Jingyan Xu, Renxiang Tan, Qinglong Guo, Hui Hui
      Abstract: CTCLs represent a rare form of non-Hodgkin’s lymphomas characterized by an accumulation of malignant CD4+ T cells in the skin. TP53 genetic alteration is one of the most prevalent genetic abnormalities in CTCLs. Therefore, it is a promising target for innovative therapeutic approaches. We found that p53 could physically interact with HDAC-1/8 and subsequently was deacetylated to lose its function in CTCL-cells, and the p53 downstream apoptosis-associated genes were repressed. Thus, the anti-CTCL activity displayed by HDAC inhibitors depends on the p53 status.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-28
      DOI: 10.1016/j.jid.2019.12.041
  • Anti-inflammatory Effects of Potassium Iodide on Sodium Dodecyl
           Sulfate-Induced Murine Skin Inflammation
    • Authors: S. Hayashi; S. Ishikawa, E. Ishii, M. Koike, T. Kaminaga, Y. Hamasaki, T. Sairenchi, G. Kobashi, K. Igawa
      Abstract: Potassium iodide (KI), initially derived from seaweed in the early 19th century, is used for treating sporotrichosis in dermatological practice. KI has also been used to treat several noninfectious inflammatory skin diseases. However, the mechanisms underlying the improvement in such skin diseases remain unknown, and KI is not used widely. Thus, although KI is an old drug, physicians may not prescribe it frequently because they lack knowledge about it. While KI is very inexpensive and causes few side effects, it has been superseded by new powerful and expensive drugs, such as biological agents.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-25
      DOI: 10.1016/j.jid.2020.01.028
  • Murine Epidermal Ceramide Synthase 4 is a Key Regulator of Skin Barrier
    • Authors: Franziska Peters; Frederik Tellkamp, Susanne Brodesser, Emmi Wachsmuth, Bettina Tosetti, Ulrike Karow, Wilhelm Bloch, Olaf Utermöhlen, Martin Krönke, Carien M. Niessen
      Abstract: Epidermal barrier dysfunction is associated with a wide range of highly prevalent inflammatory skin diseases. However, the molecular processes that drive epidermal barrier maintenance are still largely unknown. Here, using quantitative proteomics, lipidomics and mouse genetics we characterize epidermal barrier maintenance versus a newly established barrier and functionally identify differential ceramide synthase 4 (CerS4) protein expression as one key difference. We show that epidermal loss of CerS4 first disturbs epidermal lipid metabolism and adult epidermal barrier function, ultimately resulting in chronic skin barrier disease, characterized by acanthosis, hyperkeratosis, and immune cell accumulations.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-21
      DOI: 10.1016/j.jid.2020.02.006
  • Cellular, molecular and immunological characteristics of Langhans
           multinucleated giant cells programmed by IL-15
    • Authors: Hongsheng Wang; Haiqin Jiang, Rosane Teles, Yanqing Chen, Aiping Wu, Jing Lu, Zhimin Chen, Feiyang Ma, Matteo Pellegrini, Robert L. Modlin
      Abstract: Langhans multinucleated giant cells (LGCs) are a specific type of multinucleated giant cell (MGC) containing a characteristic horseshoe-shaped ring of nuclei that are present within granulomas of infectious etiology. Although cytokines that trigger macrophage activation such as IFN-γ induce LGC formation, it is not clear whether cytokines that trigger macrophage differentiation contribute to LGC formation. Here, we found that IL-15, a cytokine that induces M1 macrophage differentiation, programs human peripheral blood adherent cells to form LGCs.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-21
      DOI: 10.1016/j.jid.2020.01.026
  • Normalization Cancer Immunotherapy for Melanoma
    • Authors: Matthew D. Vesely; Lieping Chen
      Abstract: Today, we are witnessing a revolution in the treatment of cancer through the use of immunotherapy. In the last decade, work from many laboratories and clinicians have unequivocally demonstrated that the immune system can eradicate established cancers and enhance patient survival. However, immunotherapies have distinct tumor response-to-toxicity profiles due to distinct mechanisms of action. We have previously termed immunotherapies that activate a general, systemic immune response as “enhancement cancer immunotherapy” and those that target a specific dysfunctional immune response, especially within the tumor microenvironment, as “normalization cancer immunotherapy”.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-21
      DOI: 10.1016/j.jid.2020.02.005
  • TERT, BRAF, and NRAS mutational heterogeneity between paired primary and
           metastatic melanoma tumors
    • Authors: Gregory A. Chang; Jennifer M. Wiggins, Broderick C. Corless, Mahrukh M. Syeda, Jyothirmayee S. Tadepalli, Shria Blake, Nathaniel Fleming, Farbod Darvishian, Anna Pavlick, Russell Berman, Richard Shapiro, Yongzhao Shao, George Karlin-Neumann, Cindy Spittle, Iman Osman, David Polsky
      Abstract: Mutational heterogeneity can contribute to therapeutic resistance in solid cancers. In melanoma, the frequency of inter- and intra-tumoral heterogeneity is controversial. We examined mutational heterogeneity within individual melanoma patients using multi-platform analysis of commonly mutated driver and non-passenger genes.We analyzed paired primary and metastatic tumors from 60 patients, and multiple metastatic tumors from 39 patients whose primary tumors were unavailable (n=271 tumors). We used a combination of multiplex SNaPshot assays, Sanger Sequencing, Mutation-specific PCR, or droplet digital PCR to determine the presence of BRAFV600, NRASQ61, and TERT-124C>T and TERT-146C>T mutations.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-20
      DOI: 10.1016/j.jid.2020.01.027
  • A Randomized Placebo Controlled Trial of Secukinumab on Aortic Vascular
           Inflammation in Moderate to Severe Plaque Psoriasis (VIP-S)
    • Authors: Joel M. Gelfand; Daniel B. Shin, Kristina Callis Duffin, April W. Armstrong, Andrew Blauvelt, Stephen K. Tyring, Alan Menter, Scott Gottlieb, Benjamin N. Lockshin, Eric L. Simpson, Farid Kianifard, Rajendra Prasad Sarkar, Elisa Muscianisi, Jennifer Steadman, Mark A. Ahlman, Martin P. Playford, Aditya A. Joshi, Amit K. Dey, Thomas J. Werner, Abass Alavi, Nehal N. Mehta
      Abstract: Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has demonstrated high efficacy with a favorable safety profile in various psoriatic disease manifestations.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-20
      DOI: 10.1016/j.jid.2020.01.025
  • Response to Ring: In silico predictive metagenomic analyses highlight key
           metabolic pathways impacted in the HS skin microbiome
    • Authors: Andrea M. Schneider; Lauren C. Cook, Xiang Zhan, Kalins Banerjee, Zhaoyuan Cong, Yuka Imamura-Kawasawa, Samantha L. Gettle, Amy L. Longenecker, Joslyn S. Kirby, Amanda M. Nelson
      Abstract: The metagenomics analysis performed in Schneider et al provided the first investigation into the functional role of microbial dysbiosis in Hidradenitis Suppurativa (HS). This study included a predictive analysis which utilized a publically-available dataset (Ring et al. 2017) and our dataset that was generated from a prospectively recruited cohort of HS subjects and normal controls (Schneider et al. 2019). These two datasets were generated using the same sequencing method (16S rRNA V3-V4), although the patient demographics, sampling procedures, and body sites sampled varied between them (Table 1a).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-20
      DOI: 10.1016/j.jid.2020.02.003
  • Staphylococcus aureus bloodstream infection in patients with atopic
           dermatitis - or: Think twice before placing a venous catheter into
           lesional atopic skin
    • Authors: Mathé Philipp Joschua Gebhard; Joost Insa, Peyerl-Hoffmann Gabriele, Schneider Christian, Kern Winfried, Rieg Siegbert
      Abstract: Due to the high rate of colonization, patients with atopic dermatitis are at risk of S. aureus bloodstream infection, the most severe manifestation of S. aureus infections. Intravascular devices and the skin are the major portals of entry for S. aureus in AD. With prompt and adequate diagnostic and therapeutic management, mortality is lower than in Non-AD patients with SAB and severe sequelae can be averted. Important preventive strategies include AD treatment to reduce S. aureus colonization and meticulous care of intravascular catheters, which should not be placed in/on lesional atopic skin.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-18
      DOI: 10.1016/j.jid.2020.02.004
  • Next generation sequencing in myeloid neoplasm-associated Sweet’s
           syndrome demonstrates clonal relation between malignant cells and
           skin-infiltrating neutrophils
    • Authors: Marie Passet; Clémence Lepelletier, Marie-Dominique Vignon-Pennamen, François Chasset, Pierre Hirsch, Maxime Battistella, Paul Duriez, Flore Sicre de Fontbrune, Nicolas Boissel, Ollivier Legrand, Emmanuel Raffoux, Martine Bagot, Lionel Adès, Emmanuelle Clappier, Jean-David Bouaziz
      Abstract: Sweet's syndrome (SS) is a neutrophilic dermatoses (ND) that may occur in the context of malignancy, inflammatory disease or drug exposure (von den Driesch 1994). Approximately 20% of the reported SS patients have an associated cancer (Cohen et al. 1988), which is a myeloid neoplasm (MN) in half of the cases, predominantly an acute myeloid leukemia (AML) (Nelson et al. 2018). Although the association between MN and SS has been reported for a long time (Vignon-Pennamen and Wallach 1991), the pathophysiological link between these diseases remains unclear.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-18
      DOI: 10.1016/j.jid.2019.12.040
  • Lesional inflammatory profile in Hidradenitis Suppurativa is not solely
           driven by IL-1
    • Authors: A.R.J.V. Vossen; K.R. van Straalen, E.F. Florencia, E.P. Prens
      Abstract: Immune dysregulation is strongly implicated in the pathogenesis of hidradenitis suppurativa (HS).(Vossen et al., 2018) This is demonstrated by the presence of inflammation in both lesional and perilesional HS skin (Kelly et al., 2015; Van der Zee et al., 2012; Witte-Händel et al., 2019). However, our current understanding of HS pathophysiology, with follicular occlusion and rupture as the primary events, is under scrutiny. A complex immune driven pathogenesis, initiated by an initial aberrant immune response to a possibly dysbiotic cutaneous microbiome, is suspected, with follicular occlusion occurring as a secondary phenomenon.(Frew, 2019) It is presumed that commensal bacterial products like lipopolysaccharide, peptidoglycan, and bacterial DNA and RNA as well as complex keratin filaments released after follicular rupture promote the simultaneous activation of multiple auto-inflammatory pathways such as membrane and cytosolic innate receptors, complement and the NLRP inflammasome.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-18
      DOI: 10.1016/j.jid.2020.01.023
  • Loss of both CDKN2A and CDKN2B allows for centrosome overduplication in
    • Authors: Shyamal Patel; Christopher J. Wilkinson, Elena V. Sviderskaya
      Abstract: Centrosomes duplicate only once in coordination with the DNA replication cycle and have an important role in segregating genetic material. In contrast, the majority of cancer cells have centrosome aberrations including supernumerary centrosomes and this correlates with aneuploidy and genetic instability. The tumour suppressors p16 (CDKN2A) and p15 (CDKN2B) (encoded by the familial melanoma CDKN2 locus) inhibit CDK4/6 activity and have important roles in cellular senescence. p16 is also associated with suppressing centrosomal aberrations in breast cancer; however, the role of p15 in centrosome amplification is unknown.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-14
      DOI: 10.1016/j.jid.2020.01.024
  • NK cell and fibroblast-mediated regulation of skin squamous cell carcinoma
           invasion by CLEC2A is compromised in Xeroderma Pigmentosum
    • Authors: Maria Gonçalves-Maia; Yannick Gache, Miguel Basante, Estelle Cosson, Emie Salavagione, Margot Muller, Françoise Bernerd, Marie Françoise Avril, Sébastien Schaub, Alain Sarasin, Véronique M. Braud, Thierry Magnaldo
      Abstract: The ability of cancer cells to invade and disseminate can be affected by components of the surrounding microenvironment. To identify dermal components regulating the growth of epidermal carcinomas, we studied the xeroderma pigmentosum genetic disease that bears mutations in genes involved in nucleotide excision DNA repair. Xeroderma pigmentosum patients are more prone to develop cutaneous tumors compared to the general population and their dermal fibroblasts display features of dermal cancer-associated fibroblasts, promoting keratinocyte invasion.
      Citation: Journal of Investigative Dermatology ()
      PubDate: 2020-02-12
      DOI: 10.1016/j.jid.2020.01.021
  • Epidermal damage induces Th1 polarization and defines the site of
           inflammation in murine epidermolysis bullosa acquisita
    • Authors: Markus Niebuhr; Katja Bieber, David Banczyk, Sebastian Maass, Sebastian Klein, Mareike Becker, Ralf Ludwig, Detlef Zillikens, Jürgen Westermann, Kathrin Kalies
      Abstract: Epidermolysis bullosa acquisita (EBA) is an autoimmune skin disease characterized by subepidermal blisters. The pathogenesis is mediated by deposits of autoantibodies directed against type VII collagen in the skin, but the sequence of events regulating the localization of skin blisters is not fully understood. In this study, using the immunization-induced mouse model of EBA, we demonstrate that epidermal disruption induces not only an infiltration of CD4+ T cells but also a Th1 phenotype as it has been described for delayed-type hypersensitivity reactions.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-10
      DOI: 10.1016/j.jid.2020.01.022
  • COMP negatively influences keratinocyte proliferation via α5β1-integrin:
           Potential relevance of altered COMP expression in psoriasis
    • Authors: Renáta Bozó; Edit Szél, Judit Danis, Barbara Gubán, Zsuzsanna Bata-Csörgő, Kornélia Szabó, Lajos Kemény, Gergely Groma
      Abstract: In psoriasis, non-lesional skin shows alterations at the dermal–epidermal junction (DEJ) compared to healthy skin. Cartilage oligomeric matrix protein (COMP) is part of the papillary dermis of healthy skin, and its expression has not yet been studied in psoriatic skin. In this study, we found that COMP localization extended deeper into the dermis and formed a more continuous layer in psoriatic non-lesional skin compared to healthy skin, while in psoriatic lesions, COMP showed a partially discontinuous deposition at the DEJ.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-10
      DOI: 10.1016/j.jid.2019.12.037
  • Short-term exposure to a Western diet induces psoriasiform dermatitis by
           promoting accumulation of IL-17A-producing γδ T cells
    • Authors: Zhenrui Shi; Xuesong Wu, Sebastian Yu, Mindy Huynh, Prasant Kumar Jena, Mimi Nguyen, Yu-Jui Yvonne Wan, Samuel T. Hwang
      Abstract: A Western diet (WD)—characterized by its high fat and simple sugar content—is thought to predispose individuals to inflammatory skin diseases such as psoriasis, through the development of obesity. This scenario, however, is being challenged by emerging data suggesting that dietary components, rather than obesity itself, may exacerbate psoriasis. We herein show that short-term feeding with a diet analogous to the WD in mice leads to Th1/Th17-biased skin inflammation before significant body weight gain.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-09
      DOI: 10.1016/j.jid.2020.01.020
  • Imiquimod exerts antitumor effects by inducing immunogenic cell death and
           is enhanced by the glycolytic inhibitor 2-deoxy-glucose
    • Authors: Shi-Wei Huang; Sin-Ting Wang, Shu-Hao Chang, Kai-Cheng Chuang, Hsin-Yu Wang, Jun-Kai Kao, Shu-Mei Liang, Chun-Ying Wu, Shao-Hsuan Kao, Yi-Ju Chen, Jeng-Jer Shieh
      Abstract: The induction of immunogenic cell death (ICD) in cancer cells triggers specific immune responses against the same cancer cells. Imiquimod (IMQ) is a synthetic ligand of Toll-like receptor 7 that exerts antitumor activity by stimulating cell-mediated immunity or by directly inducing apoptosis. Whether IMQ causes tumors to undergo ICD and elicits a specific antitumor immune response is unknown. We demonstrated that IMQ-induced ICD-associated features, including the surface exposure of calreticulin, the secretion of ATP and HMGB1, were mediated by ROS and ER stress.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-06
      DOI: 10.1016/j.jid.2019.12.039
  • Gliadin-induced ex vivo T cell response in dermatitis herpetiformis: A
           predictor of clinical relapse on gluten challenge'
    • Authors: Suvi Kalliokoski; Eriika Mansikka, Andrea de Kauwe, Heini Huhtala, Päivi Saavalainen, Kalle Kurppa, Kaisa Hervonen, Timo Reunala, Katri Kaukinen, Teea Salmi, Katri Lindfors
      Abstract: Dermatitis herpetiformis (DH), an itchy blistering skin condition, is considered an extraintestinal manifestation of celiac disease. Both manifestations are driven by the ingestion of dietary gluten, which induces an inflammatory response hallmarked by B and T cell activation (Collin et al., 2017; du Pré and Sollid 2015). In celiac disease, the gluten-induced T cell response has been assessed by various means, including an oral three-day wheat challenge coupled with an interferon-γ (IFN-γ) enzyme-linked immunospot (ELISpot) assay (Anderson et al., 2000; Tye-Din et al., 2010a; Camarca et al., 2012; Hardy et al., 2015).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-06
      DOI: 10.1016/j.jid.2019.12.038
  • Threonine phosphorylation of IκBζ mediates inhibition of selective
           proinflammatory target genes
    • Authors: Paula Grondona; Philip Bucher, Anja Schmitt, Caroline Schönfeld, Barbara Streibl, Anne Müller, Frank Essmann, Sabrina Liberatori, Shabaz Mohammed, André Hennig, Daniela Kramer, Klaus Schulze-Osthoff, Stephan Hailfinger
      Abstract: Transcription factors of the NF-κB family play a crucial role for immune responses by activating the expression of chemokines, cytokines and antimicrobial peptides involved in pathogen clearance. IκBζ, an atypical nuclear IκB protein and selective coactivator of particular NF-κB target genes, has recently been identified as an essential regulator for skin immunity. In the present study, we discovered that IκBζ is strongly induced in keratinocytes sensing the fungal glucan zymosan A and that IκBζ is essential for the optimal expression of proinflammatory genes, such as IL6, CXCL5, IL1B or S100A9.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-06
      DOI: 10.1016/j.jid.2019.12.036
  • ATP-P2X7-induced inflammasome activation contributes to melanocyte death
           and CD8+ T-cell trafficking to the skin in vitiligo
    • Authors: Yuri Ahn; Jimyung Seo, Eun Jung Lee, Ji Young Kim, Min-Young Park, Shinwon Hwang, Abdurrahman Almurayshid, Beom Jin Lim, Je-Wook Yu, Sang Ho Oh
      Abstract: Extracellular adenosine triphosphate (ATP) is a well-known inflammasome-activating signal. Emerging evidence demonstrates a critical role for inflammasome activation in vitiligo pathogenesis. However, the specific molecular mechanism of inflammasome-dependent melanocyte degeneration in vitiligo is still not clear. This study presents how extracellular ATP, released from keratinocytes by oxidative stress, affects melanocyte survival in vitiligo skin. H2O2-induced oxidative injury increased ATP release from keratinocytes and skin tissues.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-05
      DOI: 10.1016/j.jid.2019.12.035
  • Lgr4 deletion delays the hair cycle and inhibits the activation of hair
           follicle stem cells
    • Authors: Xiaolin Ren; Weili Xia, Peng Xu, Hongyang Shen, Xing Dai, Mingyao Liu, Yuling Shi, Xiyun Ye, Yongyan Dang
      Abstract: It is known that Lgr4 plays an important role in hair follicle development, but the impact of Lgr4 on hair cycle is still unclear. In the present study, we have found that K14-Cre-mediated skin epithelia-specific deletion of Lgr4 results in delayed anagen entry during physiological hair cycle and compromised hair follicle regeneration upon transplantation. We show that while Lgr4 deletion does not appear to affect the number of quiescent hair follicle stem cells, it leads to reduced numbers of Lgr5+ and actively proliferating stem cells in the hair follicles.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-05
      DOI: 10.1016/j.jid.2019.12.034
  • Spinal GRPR and NPRA contribute to chronic itch in a murine model of
           allergic contact dermatitis.
    • Authors: Xueting Liu; De Wang, Yuhuan Wen, Liping Zeng, Yangyang Li, Tianyu Tao, Zhongqiu Zhao, Ailin Tao
      Abstract: Recurrent and intractable chronic itch is a world-wide problem but mechanisms, especially the neural mechanisms, underlying chronic itch still remain unclear. In this study, we investigated the peripheral and spinal mechanisms responsible for prolonged itch in a mouse model of allergic contact dermatitis (ACD) induced by squaric acid dibutylester (SADBE). We found that repeated exposure of mice to SADBE evoked persistent spontaneous scratching and significantly aberrant cutaneous and systemic immune responses lasting for weeks.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-05
      DOI: 10.1016/j.jid.2020.01.016
  • REDD1 (regulated in development and DNA damage 1) prevents dermal
           adipocyte differentiation and is required for hair cycle-dependent dermal
           adipose expansion
    • Authors: Guillermo C. Rivera-Gonzalez; Anna Klopot, Kaitlyn Sabin, Gleb Baida, Valerie Horsley, Irina Budunova
      Abstract: Dermal white adipose (dWAT) expansion is associated with important homeostatic and pathologic processes in skin. Even though mammalian target of Rapamycin (mTOR)/Akt signaling is important for adipogenesis, the role of regulated in development and DNA damage 1 (REDD1), a negative regulator of mTOR/Akt, is poorly understood. Loss of REDD1 in mice resulted in reduction of body mass, total fat, size of gonadal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT). Interestingly, inguinal subcutaneous WAT and dWAT in REDD1 knockouts (KOs) were expanded compared to wild type (WT) mice.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-04
      DOI: 10.1016/j.jid.2019.12.033
  • Flotillin and AP2A1/2 promote insulin-like growth factor receptor-1
           association with clathrin and internalization in primary human
    • Authors: Duncan Hieu M. Dam; Sophia A. Jelsma, Jeong Min Yu, Haoming Liu, Betty Kong, Amy S. Paller
      Abstract: Insulin-like growth factor-1 (IGF-1) receptor (IGF1R) signaling promotes keratinocyte proliferation, migration, and survival. However, the mechanism of IGF1R endocytosis in normal keratinocytes remains unclear. Confocal, super resolution structured illumination microscopy (SIM), total internal reflection fluorescence/TIRF microscopy, and coimmunoprecipitation studies reveal that IGF1R associates with flotillin-1, which currently has no known role in normal receptor tyrosine kinase endocytosis, under basal conditions in monolayer keratinocyte cultures.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-03
      DOI: 10.1016/j.jid.2020.01.015
  • Treatment with Synthetic Pseudo-Ceramide Improves Atopic Skin Switching
           the Ceramide Profile to a Healthy Skin Phenotype
    • Authors: Koichi Ishida; Akihiko Takahashi, Kotatsu Bito, Zoe Draelos, Genji Imokawa
      Abstract: Little is known about the pathophysiological linkages between altered ceramide profiles in the stratum corneum (SC) of patients with atopic dermatitis (AD) and their impaired skin barrier and water-holding functions. We studied those characteristics following topical treatment with a designed synthetic pseudo-ceramide (pCer) and analyzed that pathophysiological linkage by microanalyzing ceramides using NPLC-ESI Mass Spectrometry. Four weeks of treatment with pCer significantly reduced skin symptoms, accompanied by significant decreases in trans-epidermal water loss (TEWL) and increases in water content.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-02-01
      DOI: 10.1016/j.jid.2020.01.014
  • Interaction between Smoking and HLA-C*06:02 on the Response to Ustekinumab
           in Psoriasis
    • Authors: Axel Svedbom; Pernilla Nikamo, Mona Ståhle
      Abstract: HLA-C*06:02, is the genetic variant that affords the highest susceptibility for psoriasis, increasing the odds for the disease approximately five times (Strange et al., 2010). Its effect may be modified by a number of factors, including smoking (Jin et al., 2009).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-31
      DOI: 10.1016/j.jid.2020.01.013
  • PAR2 mediates itch via TRPV3 signaling in keratinocytes
    • Authors: Jiahui Zhao; Admire Munanairi, Xian-Yu Liu, Jie Zhang, Linghan Hu, Meiqin Hu, Dingfang Bu, Lingling Liu, Zhiqiang Xie, Brian S. Kim, Yong Yang, Zhou-Feng Chen
      Abstract: Animal studies have suggested that transient receptor potential (TRP) ion channels and G protein-coupled receptors (GPCRs) play important roles in itch transmission. TRPV3 gain-of-function mutations have been identified in patients with Olmsted syndrome which is associated with severe pruritus. However, the mechanisms causing itch remain poorly understood. Here, we show that keratinocytes lacking TRPV3 impair the function of protease activated receptor 2 (PAR2), resulting in reduced neuronal activation and scratching behavior in response to PAR2 agonists.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-28
      DOI: 10.1016/j.jid.2020.01.012
  • A Phase II, Open Label Study of Bermekimab in Patients with Hidradenitis
           Suppurativa Shows Resolution of Inflammatory Lesions and Pain
    • Authors: Alice Gottlieb; Nicola E. Natsis, Francisco Kerdel, Seth Forman, Edgar Gonzalez, Gilberto Jimenez, Liliam Hernandez, Jessica Kaffenberger, Giancarlo Guido, Kathryn Lucas, Diego Montes, Michael Gold, Chad Babcock, John Simard
      Abstract: To evaluate the safety and efficacy of bermekimab, an interleukin-1⍺ inhibitor, in the treatment of hidradenitis suppurativa (HS). Design and Setting: This study was a phase 2, multi-center, open-label study of two dose cohorts of bermekimab in patients naïve to or have failed prior anti-TNF therapy with moderate-to-severe HS.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-28
  • AURKA Enhances Autophagy of ADSCs to Promote Diabetic Wound Repair via
           Targeting FOXO3a
    • Authors: Yating Yin; Feifei Chen, Jianhua Li, Jing Yang, Qiang Li, Peisheng Jin
      Abstract: AURKA (Aurora kinase A) regulates apoptosis and autophagy in a diverse range of disease and exhibited a promising clinical efficacy. But the role of AURKA in regulating ADSCs (Adipose derived stem cells) repairing diabetic wound remains unclear. Here, we showed that ADSCs subjected to high glucose stress displayed an obvious induction of AURKA, FOXO3a and a significant increase in autophagy and apoptosis. The AURKA was confirmed to regulate autophagy through FOXO3a. AURKA mediated autophagy inhibited high glucose-induced apoptosis of ADSCs.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-28
      DOI: 10.1016/j.jid.2019.12.032
  • Apremilast in combination to narrowband UVB in the treatment of vitiligo.
           A 52 weeks monocentric prospective randomized placebo-controlled study
    • Authors: Abdallah Khemis; Eric Fontas, Sophie Moulin, Henri Montaudié, Jean-Philippe Lacour, Thierry Passeron
      Abstract: Scientific rationale and encouraging first clinical results suggest the interest of using apremilast for treating vitiligo.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-28
      DOI: 10.1016/j.jid.2019.11.031
  • Enhanced glycogen metabolism supports the survival and proliferation of
           HPV-infected keratinocytes in condylomata acuminata
    • Authors: Zhichao Gu; Huafeng Zhang, Xueyun Guo, Yuchun Cao
      Abstract: Condylomata acuminata (CA) is caused by HPV infections of keratinocytes and is a common sexually transmitted disease. The main clinical feature and risk of CA is the high recurrence of genital warts formed by infected keratinocytes. Metabolic reprogramming of most types of mammalian cells including keratinocytes can provide energy and intermediates essential for their survival. Here we report that HPV infection develops a hypoxic microenvironment in CA warts, inducing the accumulation of glycogen and increased glycogen metabolism in the infected keratinocytes in a HIF-1α dependent pathway.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-28
      DOI: 10.1016/j.jid.2020.01.010
  • Integrating Next Generation Sequencing with Morphology Improves Prognostic
           and Biologic Classification of Spitz Neoplasms
    • Authors: Victor L. Quan; Bin Zhang, Yongzhan Zhang, Lauren S. Mohan, Katherine Shi, Annette Wagner, Lacey Kruse, Timothy Taxter, Nike Beaubier, Beaubier, Kevin White, Lihua Zou, Pedram Gerami
      Abstract: The newest WHO classification suggests eliminating cases with BRAF and NRAS mutations from the categories of Spitz tumors (ST) and Spitz melanoma (SM). We aimed to better characterize the genomics of Spitz neoplasms and assess whether integrating genomic data with morphologic diagnosis improves classification and prognostication. We performed DNA and RNA sequencing on 80 STs, 26 SMs, and 22 melanomas with Spitzoid features (MSF). NGS data was used to reclassify tumors by moving BRAF/NRAS-mutated cases to MSF.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-28
      DOI: 10.1016/j.jid.2019.12.031
  • Long non-coding RNA GAS5 regulates macrophage polarization and diabetic
           wound healing
    • Authors: Junyi Hu; Liping Zhang, Cole Liechty, Carlos Zgheib, Maggie M. Hodges, Kenneth W. Liechty, Junwang Xu
      Abstract: A central feature of diabetic wounds is the persistence of chronic inflammation, which is partly due to the prolonged presence of pro-inflammatory (M1) macrophages. Using in vivo and in vitro analyses, we have tested the hypothesis that lncRNA GAS5 (Growth Arrest-Specific 5) is dysregulated in diabetic wounds. We have assessed the contribution of GAS5 to the M1 macrophage phenotype, as well as the functional consequences of knocking down its expression. We found that expression of GAS5 is significantly increased in diabetic wounds and in cells isolated from diabetic wounds.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-28
      DOI: 10.1016/j.jid.2019.12.030
  • Wif1 suppresses the generation of suprabasal cells in acanthotic skin and
           growth of basal cell carcinomas upon forced overexpression
    • Authors: Marco Becker; Julia Bauer, Joanna Pyczek, Simone König, Anna Müllen, Hanna Rabe, Michael P. Schön, Anja Uhmann, Heidi Hahn
      Abstract: We analyzed the role of Wnt inhibitory factor 1 (Wif1) in normal and acanthotic epidermis of 12-O-tetradecanoylphorbol-13-acetate (TPA) or all-trans-retinoic acid (ATRA)-treated and basal cell carcinoma (BCC)-bearing mice. Wif1 protein is located in the follicular infundibulum and interfollicular epidermis (IFE) in murine back skin. Within the hyperplastic epidermis of TPA- or ATRA-treated or BCC-bearing murine skin, Wif1 and K10 overlap in Ki67neg suprabasal layers, while basal epidermal layers expressing Ki67, and BCCs expressing Wif1 mRNA, are free of Wif1 protein.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-24
      DOI: 10.1016/j.jid.2019.11.030
  • Palmoplantar keratoderma with leukokeratosis anogenitalis caused by KDSR
    • Authors: Marcel Huber; Elena Chiticariu, Daniel Bachmann, Lukas Flatz, Daniel Hohl
      Abstract: Hereditary keratodermas and ichthyoses comprise a large collection of genodermatoses for which underlying mutations in more than 100 genes have been identified (Oji et al., 2010). The implicated genes are involved in a multitude of biological pathways. Ceramides are important for cutaneous barrier function (Borodzicz et al., 2016) and cutaneous proliferation and differentiation (Uchida, 2014). In most organisms they are synthesized by three different biochemical pathways, named de novo, sphingomyelinase and salvage pathways (Hannun and Obeid, 2008, Kihara, 2016, Kitatani et al., 2008).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-24
      DOI: 10.1016/j.jid.2019.11.029
  • Phenotypic plasticity of cutaneous squamous cell carcinoma mediated by
    • Authors: Hyeongsun Moon; Dahihm Kim, Leanne R. Donahue, Andrew C. White
      Abstract: To the Editor, Squamous cell carcinomas (SCCs) are the most common type of cancer capable of metastasis (Yan et al., 2011). The enzymatic activity of Cox-2 (Cyclooxygenase 2, also called Ptgs2), contributes to the synthesis of prostanoids and is upregulated in numerous types of cancers, including cutaneous SCCs (cSCCs) (Subbaramaiah and Dannenberg, 2003; Sobolewski et al., 2010; Hua et al., 2015). Cox-2 is an important regulator of tumor development and progression in ultraviolet and chemical carcinogenesis models of cSCC (Jiao et al., 2014b; a; Elmets, Ledet and Athar, 2014).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-22
      DOI: 10.1016/j.jid.2019.12.028
  • Human Polyomavirus 6 with the Asian/Japanese Genotype in Cases of Kimura
           Disease and Angiolymphoid Hyperplasia with Eosinophilia
    • Authors: Yumiko Hashida; Tomonori Higuchi, Kimiko Nakajima, Takako Ujihara, Ichiro Murakami, Mikiya Fujieda, Shigetoshi Sano, Masanori Daibata
      Abstract: Some human polyomaviruses (HPyVs) have been associated with inflammatory skin conditions (Ho et al., 2015; Nguyen et al, 2017). More investigation is needed to identify further presentations of pathological cases of patients with cutaneous HPyVs (Nguyen et al., 2019; Sheu et al., 2019). Kimura disease (KD) is a rare form of chronic inflammatory disorder involving subcutaneous tissue, and frequently associated with regional lymphadenopathy (Leiferman and Peters, 2018). KD is seen predominantly in East Asian populations, especially Japanese and Chinese individuals (Chen et al., 2004; Long et al., 2016), but the underlying cause is still unknown.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-22
      DOI: 10.1016/j.jid.2019.12.027
  • Identification of a human skin commensal bacterium that selectively kills
           Cutibacterium acnes
    • Authors: Alan M. O’Neill; Teruaki Nakatsuji, Asumi Hayachi, Michael R. Williams, Robert H. Mills, David J. Gonzalez, Richard L. Gallo
      Abstract: The microbiome represents a vast resource for drug discovery as its members engage in constant conflict to outcompete one another by deploying diverse strategies for survival. Cutibacterium acnes (C. acnes) is one of the most common bacterial species on human skin and can promote the common disease acne vulgaris. By employing a combined strategy of functional screening, genetics and proteomics we discovered a strain of Staphylococcus capitis (S. capitis E12) that selectively inhibited growth of C.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-22
      DOI: 10.1016/j.jid.2019.12.026
  • Association of HLA-A*11:01 with sulfonamide-related severe cutaneous
           adverse reactions in Japanese patients
    • Authors: Ryosuke Nakamura; Takeshi Ozeki, Noriaki Hirayama, Akihiro Sekine, Taiki Yamashita, Yoichi Mashimo, Yoshiko Mizukawa, Tetsuo Shiohara, Hideaki Watanabe, Hirohiko Sueki, Kohei Ogawa, Hideo Asada, Nahoko Kaniwa, Eri Tsukagoshi, Kayoko Matsunaga, Hiroyuki Niihara, Yukie Yamaguchi, Michiko Aihara, Taisei Mushiroda, Yoshiro Saito, Eishin Morita
      Abstract: Sulfonamides are pharmaceuticals with an SO2-NH2 group, used mainly for treating infectious and inflammatory diseases. Their main active ingredient is sulfanilamide (SN), a metabolite that can inhibit folic acid synthesis in bacteria. In Japan, common sulfonamides include sulfamethoxazole (SMX) and salazosulfapyridine (SASP). Sulfonamides can cause severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DIHS) (Schnyder and Pichler, 2013).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-22
      DOI: 10.1016/j.jid.2019.12.025
  • Ciliation index is a useful diagnostic tool in challenging spitzoid
           melanocytic neoplasms
    • Authors: Ursula E. Lang; Rodrigo Torres, Christine Cheung, Eszter K. Vladar, Timothy H. McCalmont, Jinah Kim, Robert L. Judson-Torres
      Abstract: The loss of primary cilia on melanocytes is a useful biomarker for the distinction of melanoma from conventional melanocytic nevi. It is unknown whether ciliation status is beneficial for diagnosing spitzoid tumors - a subclass of melanomas that present inherently ambiguous histology and are challenging to classify. We evaluated ciliation index (CI) in 68 cases of spitzoid tumors ranging from Spitz nevi (SN) and atypical Spitz tumors (AST) to spitzoid melanoma (SM). We found a significant decrease in CI within the SM group when compared to either the SN or AST groups.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-22
      DOI: 10.1016/j.jid.2019.11.028
  • RNase 7 promotes sensing of self-DNA by human keratinocytes and activates
           an antiviral immune response.
    • Authors: V. Kopfnagel; S. Dreyer, K. Baumert, M. Stark, J. Harder, K. Hofmann, M. Kleine, A. Buch, B. Sodeik, T. Werfel
      Abstract: RNase 7 is one of the major antimicrobial peptides (AMPs) secreted by keratinocytes. The AMPs hBD-2 and LL-37 promote TLR9-mediated activation of human plasmacytoid dendritic cells (pDCs) by human self-DNA; however, whether keratinocytes respond in a similar way has not yet been addressed. Keratinocytes express several receptors for the detection of cytosolic DNA. Here, we investigated the activation of keratinocytes by RNase 7 in combination with human DNA. Stimulation of keratinocytes with RNase 7 and human DNA induced a strong increase of IP-10 production.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-21
      DOI: 10.1016/j.jid.2019.09.029
  • Bathing Does Not Facilitate The Human Skin Penetration Or Adverse Cellular
           Effects Of Nanoparticulate Zinc Oxide Sunscreens After Topical Application
    • Authors: Yousuf H. Mohammed; Isha N. Haridass, Jeffrey E. Grice, Heather A.E. Benson, Michael S. Roberts
      Abstract: To the Editor, The regular use of sunscreen products protects against sunburn, photo-aging and skin cancer (Waldman and Grant-Kels, 2019). A recent Australasian Sunscreen Summit recommended that sunscreens should be applied daily when the UV index is expected to be 3 or more to decrease future skin cancer incidence (Whiteman et al., 2019). However, although Australia has one of the highest rates of skin cancer in the world, only 55 percent of Australians believed it was safe to use sunscreen every day (Cancer Council Australia, 2017).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-21
      DOI: 10.1016/j.jid.2019.12.024
  • RAB27A/Melanophilin blocker inhibits melanoma cell motility and invasion.
    • Authors: Dajiang Guo; Rohit Jain, Jae Sung Hwang, Wolfgang Weninger, Kimberley A. Beaumont, Shweta Tikoo
      Abstract: Melanoma is cancer caused by the neoplastic transformation of melanocytes. The last decade has witnessed a surge in treatment options for advanced melanoma patients, especially immunotherapeutic interventions; nonetheless, issues such as drug resistance, limited efficacy, and high-toxicity ensue (Luke et al., 2017). Understanding the mechanisms underpinning melanoma progression and invasion is, therefore, vital for the development of treatment strategies.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-21
      DOI: 10.1016/j.jid.2019.12.023
  • The phosphatase regulator NIPP1 restrains chemokine-driven skin
    • Authors: Iris Verbinnen; Marloes Jonkhout, Kifayathullah Liakath-Ali, Kathelijne Szekér, Mónica Ferreira, Shannah Boens, Raphael Rouget, Margareta Nikolic, Susan Schlenner, Aleyde Van Eynde, Mathieu Bollen
      Abstract: NIPP1 is a ubiquitously expressed nuclear protein that regulates functions of protein Ser/Thr phosphatase-1 in cell proliferation and lineage specification. The role of NIPP1 in tissue homeostasis is not fully understood. Here we show that the selective deletion of NIPP1 in mouse epidermis resulted in epidermal hyperproliferation, a reduced adherence of basal keratinocytes and a gradual decrease in the stemness of hair follicle stem cells, culminating in hair loss. This complex phenotype was associated with chronic sterile skin inflammation and could be partially rescued by dexamethasone treatment.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-20
      DOI: 10.1016/j.jid.2020.01.008
  • Molecular and Cellular Responses to the TYK2/JAK1 Inhibitor, PF 06700841,
           Reveal Reduction of Skin Inflammation in Plaque Psoriasis
    • Authors: Karen M. Page; Mayte Suarez-Farinas, Maria Suprun, Weidong Zhang, Sandra Garcet, Judilyn Fuentes-Duculan, Xuan Li, Matthew Scaramozza, Elizabeth Kieras, Christopher Banfield, James D. Clark, Andrew Fensome, James G. Krueger, Elena Peeva
      Abstract: The interleukin (IL)-23/T-helper type 17 cell axis is a target for psoriasis. The tyrosine kinase 2 (TYK2)/Janus kinase 1 (JAK1) inhibitor, PF-06700841, will directly suppress TYK2-dependent IL-12 and IL-23 signaling and JAK1-dependent signaling in cells expressing these signaling molecules, including T cells and keratinocytes. This clinical study sought to define the inflammatory gene and cellular pathways through which PF-06700841 improves the clinical manifestations of psoriasis. Patients (n=30) with moderate-to-severe psoriasis were randomized to once-daily 30 mg (n=14) or 100 mg (n=7) PF-06700841, or placebo (n=9) for 28 days.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-20
      DOI: 10.1016/j.jid.2019.11.027
  • Specific IgA and CLA+ T-cell IL-17 response to Streptococcus pyogenes in
    • Authors: Carmen De Jesús-Gil; Lidia Sans-de San Nicolás, Ester Ruiz-Romeu, Marta Ferran, Laura Soria-Martinez, Anca Chiriac, Antonio Celada, Ramon M. Pujol, Luis F. Santamaria-Babí
      Abstract: Streptococcus pyogenes tonsillar infection is well-known to trigger and exacerbate psoriasis lesions in both guttate and plaque forms of the disease. Although mucosal and cutaneous tissues are closely involved in psoriasis pathology, the interaction between their specific immune responses has not been deeply explored. This work aims to address and characterize the presence of humoral responses against Streptococcus pyogenes in psoriasis patients and its putative association with cytokine responses detected in vitro in our psoriasis ex vivo model, based on the coculture of CLA+/- T cells with autologous epidermal cells.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-20
      DOI: 10.1016/j.jid.2019.12.022
  • Activated Hgf-Met signaling cooperates with oncogenic Braf to drive
           primary cutaneous melanomas and angiotropic lung metastases in mice
    • Authors: Andreas Dominik Braun; Miriam Mengoni, Susanne Bonifatius, Thomas Tüting, Evelyn Gaffal
      Abstract: Oncogenic mutations in the Braf-kinase gene represent the most frequent genomic driver in acquired melanocytic nevi and in cutaneous melanomas. It is currently thought that oncogene-induced senescence and cell cycle arrest limit the ability of oncogenic Braf to promote melanocyte proliferation in benign nevi. The molecular and cellular mechanisms that allow an oncogenic Braf mutation to fully transform melanocytes into invasively growing melanoma cells that are able to metastasize systemically are only partially understood.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-20
      DOI: 10.1016/j.jid.2019.12.020
  • IL-17E (IL-25) and IL-17A differentially affect the functions of human
    • Authors: Julia Borowczyk; Claudia Buerger, Neschaat Tadjrischi, Justyna Drukala, Michal Wolnicki, Dawid Wnuk, Ali Modarressi, Wolf-Henning Boehncke, Nicolò Costantino Brembilla
      Abstract: Our group has recently shown that keratinocyte-derived IL-17E (IL-25), one of six members of the IL-17 family, is overexpressed in lesional psoriatic skin and is involved in its pathophysiology. We show here that IL-22 enhances IL-17E production in human keratinocytes and that these cells display a complete IL-17E receptor at their surface, which expression is further induced by IL-17A, indicating a potential autocrine effect of IL-17E. Therefore, we addressed the impact of IL-17E on the function of human primary keratinocytes.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-18
      DOI: 10.1016/j.jid.2019.12.013
  • Epidermolysis Bullosa Simplex keratinocytes show disturbed mitochondrial
           positioning and activity
    • Authors: Alyssa Vetter; Kristin Jahn, Jamal-Eddine Bouameur, Dimitra Kiritsi, Thomas M. Magin
      Abstract: TO THE EDITOR
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-17
  • Activation of SIRT1 Enhances Epidermal Permeability Barrier Formation
           Through Ceramide Synthases 2 and 3-Dependent Mechanisms
    • Authors: Kyong-Oh Shin; Chae-Jin Lim, Hye Yoon Park, Sungeun Kim, Bogyeong Kim, Yerin Lee, Hwajee Chung, Se-Kyoo Jeong, Keedon Park, Kyungho Park
      Abstract: We recently demonstrated that a synthetic silent information regulator T1 (SIRT1) activator, Hexacarboxymethyldipeptide-12 (HMD-12), protects the skin against damages caused by ultraviolet irradiation (Lim et al., 2017). In addition, in one study, SIRT1 activation has been shown to promote keratinocyte (KC) differentiation, which is a critical process for the formation of the epidermal barrier, but the cellular mechanism underlying the SIRT1-mediated KC differentiation has remained unknown (Blander et al., 2009).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-17
      DOI: 10.1016/j.jid.2019.12.021
  • JAK inhibition prevents bleomycin-induced fibrosis in mice and is
           effective in morphea patients
    • Authors: William Damsky; Dhrumil Patel, Colton J. Garelli, Madhuri Garg, Alice Wang, Karen Dresser, April Deng, John E. Harris, Jillian Richmond, Brett King
      Abstract: To the Editor, Morphea is an autoimmune disease that causes fibrosis of the skin that may result in significant morbidity. Eosinophilic fasciitis (EF) may be considered a deeper form of morphea, and features of both morphea and EF can be present in individual patients. Morphea and EF have been postulated to have pathogenic features that overlap with systemic sclerosis (Laxer and Zulian, 2006). In these diseases, dysregulated immune responses are thought to induce fibrosis (Torok et al., 2019). Treatment of these diseases with non-specific immunosuppressants such as corticosteroids is often ineffective and associated with toxicity.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-16
      DOI: 10.1016/j.jid.2019.12.019
  • Decreased CCN3 in Systemic Sclerosis endothelial cells contributes to
           impaired angiogenesis
    • Authors: Pauline Henrot; François Moisan, Paôline Laurent, Pauline Manicki, Priscilla Kaulanjan-Checkmodine, Valérie Jolivel, Hamid Reza Rezvani, Vaianu Leroy, François Picard, Carine Boulon, Thierry Schaeverbeke, Julien Seneschal, Estibaliz Lazaro, Alain Taïeb, Marie-Elise Truchetet, Muriel Cario
      Abstract: Systemic sclerosis (SSc) is a rare and severe connective tissue disease combining auto-immune and vasculopathy features, ultimately leading to organ fibrosis. Impaired angiogenesis is an often silent and life-threatening complication of the disease. We hypothesize that CCN3 (NOV), a member of the CCN family of extra-cellular matrix proteins, which is an antagonist of the pro-fibrotic protein CCN2 (CTGF) as well as a pro-angiogenic factor, is implicated in SSc pathophysiology.We performed skin biopsies on 26 SSc patients, both in fibrotic and non-fibrotic areas for 17 patients, and collected 18 healthy control skin specimens, for immunohistochemistry and cell culture.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-16
      DOI: 10.1016/j.jid.2019.11.026
  • B cell-targeted immunotherapy limits tumor growth, enhances survival and
    • Authors: Lai-Fong Kok; Angela L. Ferguson, Jacqueline E. Marshall, Benita C.Y. Tse, Gary M. Halliday, Scott N. Byrne
      Abstract: Ultraviolet (UV)-induced DNA damage, suppression of anti-tumor immune responses and promotion of cutaneous inflammation underly the skin tumor promoting activities of sunlight. Targeting the immune regulatory pathways activated by UV is proving a highly effective therapeutic strategy to treat both melanoma (Hodi et al., 2010) and keratinocyte cancers (Day et al., 2017). However, many of these first generation check-point inhibitors come with significant side effects including increased risk of autoimmune toxicities (Phan et al., 2003) and rejection of allografts in some transplant recipients at high risk of metastatic skin cancer (Abdel-Wahab et al., 2019).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-16
      DOI: 10.1016/j.jid.2019.12.018
  • MDA5+ Dermatomyositis Is Associated with Stronger Skin Type I Interferon
           Transcriptomic Signature with Upregulation of IFN-κ Transcript
    • Authors: Charles Cassius; Reyhan Amode, Marc Delord, Maxime Battistella, Justine Poirot, Alexandre How-Kit, Clémence Lepelletier, Marie Jachiet, Adèle de Masson, Laure Frumholtz, Florence Cordoliani, David Boccara, Jacqueline Lehmann-Che, Jennifer Wong, Sylvie Dubanchet, Antonio José Alberdi, Marine Merandet, Martine Bagot, Armand Bensussan, Jean-David Bouaziz, Hélène Le Buanec
      Abstract: Dermatomyositis (DM) is a chronic inflammatory and autoimmune disorder belonging to the idiopathic inflammatory myopathies affecting primarily skin and muscle with variable extent. Disease mechanism comprehension is growing, with a pivotal role of both the innate and adaptive immune system and involvement of both cellular and humoral actors (Nagaraju and Lundberg, 2011). The immune transcriptomic signature of DM is characterized by a type I IFN signature in peripheral blood mononuclear cells, muscle, and skin, which has been shown to correlate with disease activity (Baechler et al., 2011; Walsh et al., 2007; Wong et al., 2012); consequently, targeting type I IFN seems to represent a novel therapeutic approach in DM (Higgs et al., 2014).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-16
  • The value of item banks, CAT and PROMIS for dermatology
    • Authors: Caroline B. Terwee
      Abstract: Patient-Reported Outcome Measures (PROMs) have been used in research for decades. Increasingly PROMs are being used in clinical practice to systematically address, and monitor over time, how patients feel and function in daily life. Using PROMs empowers patients to discuss health issues, which improves communication and contributes to informed decision making, in line with the principles of delivering value-based health care (Rotenstein et al., 2017).
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-13
      DOI: 10.1016/j.jid.2019.12.017
  • Rare loss-of-function mutation in SERPINA3 in generalized pustular
    • Authors: Silke Frey; Heinrich Sticht, Dagmar Wilsmann-Theis, Anne Gerschütz, Katharina Wolf, Sabine Löhr, Stefan Haskamp, Benjamin Frey, Madelaine Hahn, Arif B. Ekici, Steffen Uebe, Christian Thiel, André Reis, Harald Burkhardt, Frank Behrens, Michaela Köhm, Jürgen Rech, Georg Schett, Gunter Assmann, Külli Kingo, Sulev Kõks, Rotraut Mössner, Jörg C. Prinz, Vinzenz Oji, Peter Schulz, Luis E. Muñoz, Andreas E. Kremer, Jörg Wenzel, Ulrike Hüffmeier
      Abstract: Generalized pustular psoriasis (GPP) represents a rare pustular disease manifesting as a multi-systemic inflammation in a chronic or episodic course, sometimes as life-threatening incidents. Bi-allelic IL36RN mutations are known to be disease-causing/ -contributing in 21-41% of GPP patients (Hussain et al., 2015, Marrakchi et al., 2011, Mossner et al., 2018, Onoufriadis et al., 2011, Sugiura et al., 2013). IL-36 binds to the IL-36-receptor(IL-36R)-complex, thereby triggering the activation of MAPK and NF-κB, resulting in production of pro-inflammatory cytokines.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-13
      DOI: 10.1016/j.jid.2019.11.024
  • Differences in staining for neutrophil elastase and its controlling
           inhibitor SLPI reveal heterogeneity among neutrophils in psoriasis.
    • Authors: Joanna Skrzeczynska-Moncznik; Katarzyna Zabieglo, Oktawia Osiecka, Agnieszka Morytko, Piotr Brzoza, Lukasz Drozdz, Monika Kapinska-Mrowiecka, Brice Korkmaz, Maciej Pastuszczak, Joanna Kosalka-Wegiel, Jacek Musial, Joanna Cichy
      Abstract: Neutrophils are broadly classified into conventional neutrophils (PMNs) and low density granulocytes (LDGs). LDGs are better than PMNs in the generation of NETs, which may contribute to the pathology of autoimmune diseases. We hypothesized that LDGs and PMNs differ in levels of unrestrained neutrophil elastase (NE) that supports NET generation. Here, we show that individuals with psoriasis contain elevated levels of LDGs and that in contrast to PMNs, LDGs display higher staining for NE and lower staining for its inhibitor SLPI.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-13
      DOI: 10.1016/j.jid.2019.12.015
  • Calcium-inducible MAPK/AP-1 signaling drives semaphorin 3A expression in
           normal human epidermal keratinocytes
    • Authors: Yayoi Kamata; Mitsutoshi Tominaga, Yoshie Umehara, Kotaro Honda, Atsuko Kamo, Catharina Sagita Moniaga, Eriko Komiya, Sumika Toyama, Yasushi Suga, Hideoki Ogawa, Kenji Takamori
      Abstract: Epidermal keratinocytes express semaphorin (Sema) 3A, which is involved in the regulation of cutaneous innervation. However, the mechanisms underlying the intracellular signaling of Sema3A expression in keratinocytes remain unknown. We herein investigated signaling mechanisms for the induction of Sema3A expression in normal human epidermal keratinocytes (NHEKs). Sema3A expression transiently increased in calcium-stimulated NHEKs, but markedly decreased in terminally differentiated NHEKs. Sema3A mRNA mainly localized in the stratum basale and stratum suprabasale of the epidermis.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-13
      DOI: 10.1016/j.jid.2020.01.001
  • A small molecule CCR2 antagonist depletes tumor macrophages and synergizes
           with anti-PD1 in a murine model of cutaneous T cell lymphoma (CTCL)
    • Authors: Xuesong Wu; Rajinder Singh, Daniel K. Hsu, Yan Zhou, Sebastian Yu, Dan Han, Zhenrui Shi, Mindy Huynh, James J. Campbell, Sam T. Hwang
      Abstract: Tumor-associated macrophages (TAMs) recruited from blood monocytes are key in establishing an immunosuppressive tumor microenvironment (TME) for supporting tumor growth. We hypothesize that blocking monocyte trafficking (through inhibition of specific chemokine receptors) into skin can influence tumor development. Herein, we examine the effects of oral administration of a small molecule inhibitor for CCR2, CCR2i, which blocks CCR2-mediated chemotaxis of monocytes in a syngeneic mouse T cell lymphoma in skin.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-13
      DOI: 10.1016/j.jid.2019.11.018
  • Steroid receptor RNA activator (SRA), a long noncoding RNA, activates p38,
           facilitates epithelial mesenchymal transformation, and experimental
           melanoma metastasis
    • Authors: Chien-Hui Hong; Ji-Chen Ho, Chih-Hung Lee
      Abstract: Melanoma metastasis signals dismal prognosis even with current checkpoint inhibitors. Long noncoding RNAs (lncRNAs) regulate dynamic metastasis in several cancers, including melanoma. We become interested in a lncRNA, SRA (steroid receptor RNA activator), because it is the first lncRNA also encoding a conserved protein SRAP and regulates progression of prostate and breast cancers. We investigated how SRA mediates melanoma proliferation, migration, invasion, EMT, and metastasis by RNA interference.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-13
      DOI: 10.1016/j.jid.2019.09.028
  • MiR-101-3p down-regulates TLR2 expression, leading to reduction in
           cytokines production by T. pallidum-stimulated macrophages
    • Authors: Tao Huang; Jieyi Yang, Jun Zhang, Wujian Ke, Fei Zou, Chengsong Wan, Liuyuan Wang, Xiaohui Zhang, Fangwen Liang, Shuqing Mei, Qiwei Zhang, Zhili Rong, Bin Yang, Heping Zheng
      Abstract: Treponema pallidum (Tp) infection-induced immune responses can cause tissue damage. However, the underlying mechanism by which Tp infection induces immune response is unclear. Recent studies suggest a regulatory role of microRNAs (miRNAs) in host immunity. We assessed whether miRNAs also have a regulatory role in immune response to Tp infection in vitro. Our results showed that miR-101-3p levels were significantly higher in peripheral blood mononuclear cells of patients with primary syphilis and those in the serofast state, while TLR2 levels were higher in syphilitic patients than in healthy controls.
      Citation: Journal of Investigative Dermatology (2020)
      PubDate: 2020-01-10
      DOI: 10.1016/j.jid.2019.12.012
  • Aryl Hydrocarbon Receptor in Cutaneous Vascular Endothelial Cells
           Restricts Psoriasis Development by Negatively Regulating Neutrophil
    • Authors: Zhenlai Zhu; Jiaoling Chen, Yiting Lin, Chen Zhang, Wei Li, Hongjiang Qiao, Meng Fu, Erle Dang, Gang Wang
      Abstract: Vascular endothelial cells (VECs) that line the interiors of blood vessels participate in physiological and inflammatory processes. All skin cell types express the aryl hydrocarbon receptor (AhR), which is involved in the pathogenesis of psoriasis. However, the role of the cutaneous VEC AhR in the pathogenesis of psoriasis remains elusive. In the present study, we found that AhR protein expression and activation were downregulated in psoriatic VECs. Furthermore, cutaneous VEC-specific AhR-knockout (AhRcVECs-KO) mice were established.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-30
      DOI: 10.1016/j.jid.2019.11.022
  • Kallikrein 7 promotes atopic dermatitis-associated itch independently of
           skin inflammation
    • Authors: Changxiong J. Guo; Madison R. Mack, Landon K. Oetjen, Anna M. Trier, Martha L. Council, Ana B. Pavel, Emma Guttman-Yassky, Brian S. Kim, Qin Liu
      Abstract: Atopic dermatitis (AD) is a highly prevalent, itchy inflammatory skin disorder that is thought to arise from a combination of defective skin barrier and immune dysregulation. Kallikreins (KLK), a family of serine proteases with a diverse array of homeostatic functions including skin desquamation and innate immunity, are speculated to contribute to AD pathogenesis. Their precise role in AD, however, has not been clearly defined. In this study, unbiased RNA-seq analyses identified KLK7 as the most abundant and differentially expressed KLK in both human AD and murine AD-like skin.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-26
  • Cutaneous T-cell lymphoma (CTCL) cell line-derived extracellular vesicles
           contain HERV-W-encoded fusogenic syncytin-1.
    • Authors: Kirsi Laukkanen; Mirjam Saarinen, Francois Mallet, Maria Aatonen, Annika Hau, Annamari Ranki
      Abstract: We have previously shown that HERV-W-encoded fusogenic membrane protein syncytin-1 plays a role in the pathogenesis of mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma (CTCL; Maliniemi et al., 2013). The expression of syncytin-1 protein was detected in 15 of 30 MF skin lesions but not in skin-homing non-malignant lymphocytes. Primary cutaneous CD30-positive lymphoproliferative disorders, including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL), are the second most common form of CTCLs and represent approximately 25% of all CTCLs (Willemze et al., 2019; Nikolaenko et al., 2019).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-26
      DOI: 10.1016/j.jid.2019.11.021
  • Analysis of skin-resident memory T cells following drug hypersensitivity
    • Authors: J.A. Trubiano; C.L. Gordon, C. Castellucci, S.N. Christo, S.L. Park, E. Mouhtouris, K. Konvinse, M. Rose, M. Goh, A.S. Boyd, E.J. Phillips, L.K. Mackay
      Abstract: Tissue-resident memory T (TRM) cells persist in peripheral tissues such as skin and do not recirculate (Mueller and Mackay, 2016). TRM cells protect against infections and mediate anti-tumor responses, but have also been implicated in driving autoimmune and other immune-mediated diseases (Masopust and Soerens, 2019),(Park and Kupper, 2015). However, relatively little is known about their role in mediating delayed drug hypersensitivity reactions. Studies of cutaneous drug reactions such as fixed drug eruption that involve recurrent lesions at the same site after re-exposure to the offending agent, have indicated that localised skin TRM cells may be mediating inflammatory responses (Shiohara et al., 2002).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-26
      DOI: 10.1016/j.jid.2019.11.020
  • Melanin has a small inhibitory effect on cutaneous vitamin D synthesis: a
           comparison of extreme phenotypes
    • Authors: Antony R. Young; Kylie A. Morgan, Tak-Wai Ho, Ngozi Ojimba, Graham I. Harrison, Karl P. Lawrence, Nihull Jakharia-Shah, Hans Christian Wulf, J Kennedy Cruickshank, Peter A. Philipsen
      Abstract: Epidemiology suggests that melanin inhibits cutaneous vitamin D3 synthesis by solar ultraviolet radiation (UVR). Laboratory investigations assessing the impact of melanin on vitamin D production have given contradictory results. We determined the effect of melanin on vitamin D3 photosynthesis in healthy young volunteers (n=102) of Fitzpatrick skin types II-VI (white to black). Participants, irrespective of skin type, were exposed to the same sub-erythemal UVR dose, to 85% body surface area, using solar simulated UVR or narrowband UVB (311nm).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-26
      DOI: 10.1016/j.jid.2019.11.019
    • Authors: Benoit Arveiler; Vincent Michaud, Eulalie Lasseaux
      Abstract: Albinism is a clinically and genetically heterogeneous condition characterized by variable degrees of hypopigmentation extending from a complete absence of pigmentation to a normal pigmentation, and by ophthalmological anomalies including nystagmus, foveal hypoplasia, chiasmatic misrouting of the optic nerves, iris transillumination, retinal hypopigmentation and reduced visual acuity. 19 genes are involved in the oculocutaneous, ocular and syndromic (Hermansky-Pudlak Syndrome and Chediak-Higashi Syndrome) forms of the disease and in the more recently characterized FHONDA (Foveal Hypoplasia, Optic Nerve Decussation defects and Anterior segment dysgenesis) (Montoliu et al., 2014; Arveiler et al., 2017).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-26
      DOI: 10.1016/j.jid.2019.12.010
  • Engineered Fibronectin Peptide Resists Elastase Digestion, Speeds Healing,
           and Attenuates Scarring in Porcine Burns
    • Authors: Fubao Lin; Atulya Prasad, Samantha Weber-Fishkin, Richard A. Clark
      Abstract: TO THE EDITOR (text = 1000 words)
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-26
  • Skin-selective CD8 T cell depletion by photoimmunotherapy inhibits human
           cutaneous acute graft-versus-host disease
    • Authors: Lukas Freund; Stephanie Oehrl, Galina Gräbe, Patrick Gholam, Thomas Plum, Knut Schäkel
      Abstract: T cells play a central role in the pathogenesis of different inflammatory skin diseases. Although systemic antibody-directed depletion of lymphocytes has proven therapeutically effective, it causes considerable immune suppression. Therefore, skin-selective T cell depletion strategies may appear as a promising approach. We demonstrate that the skin-selective depletion of CD8 T cells can be achieved by specific antibody binding and activation of a conjugated photosensitizer (IRDye 700DX) by near-infrared (NIR).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-24
      DOI: 10.1016/j.jid.2019.12.009
  • Reduction in human epidermal Langerhans cells with age is associated with
           decline in CXCL14-mediated recruitment of CD14+ monocytes
    • Authors: Tatsuya Hasegawa; Zhaoyi Feng, Zhiyu Yan, Kenneth H. Ngo, Junichi Hosoi, Shadmehr Demehri
      Abstract: Skin provides the first line of physical and immunological defense against the environmental insults. However, the age-related changes in the immune function of the human skin are unclear. Here, we investigated the age-related changes in epidermal Langerhans cells (LCs), which play a sentinel role in the initiation of the immune responses in the skin. We found a significant reduction in the number of epidermal LCs in the sun-protected skin with age. Among the possible explanations for this reduction, we found that the number of CD14+ CD207+ CCR6+ dermal-resident monocytes that can differentiate into epidermal LCs were markedly reduced with age (p = 0.0057).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-24
      DOI: 10.1016/j.jid.2019.11.017
  • Unexpected High Levels of BRN2/POU3F2 Expression in Human Dermal
           Melanocytic Nevi
    • Authors: Arash Chitsazan; Duncan Lambie, Blake Ferguson, Herlina Y. Handoko, Brian Gabrielli, Graeme J. Walker, Glen M. Boyle
      Abstract: Malignant melanoma (MM) is the most aggressive skin cancer. The majority of cancer associated deaths are due to invasion of cancer cells to distant tissues. It is thus of great importance to understand the mechanisms of metastatic spread. A potential marker for this is BRN2, encoded by the POU3F2 gene, that interacts with SOX transcription factors (Cook and Sturm, 2008, Malik et al., 2018). While some studies consider BRN2 as a positive regulator of MITF, which favours proliferation (Goodall et al., 2004a, Wellbrock et al., 2008), other studies propose a dual function for BRN2 in both tumour proliferation and invasion, which could be controlled via up/down regulation of MITF respectively (Simmons et al., 2017, Wellbrock and Arozarena, 2015).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-24
      DOI: 10.1016/j.jid.2019.12.007
  • Staphylococcus aureus colonization is increased on lupus skin lesions and
           is promoted by interferon-mediated barrier disruption
    • Authors: Sirisha Sirobhushanam; Navya Parsa, Tamra J. Reed, Celine C. Berthier, Mrinal K. Sarkar, Grace A. Hile, Lam C. Tsoi, Josh Banfield, Craig Dobry, Alexander R. Horswill, Johann E. Gudjonsson, J. Michelle Kahlenberg
      Abstract: Cutaneous inflammation is recurrent in systemic lupus erythematosus (SLE), yet mechanisms that drive cutaneous inflammation in SLE are not well-defined. Type I IFNs are elevated in non-lesional SLE skin and promote inflammatory responses. Staphylococcus aureus, known to induce IFN production, could play a role in cutaneous inflammation in SLE. We show here that active cutaneous lupus erythematosus (CLE) lesions are highly colonized (∼50%) by S. aureus. To define the impact of IFNs on S. aureus colonization, we examined the effects of type I and type II IFNs on S.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-23
      DOI: 10.1016/j.jid.2019.11.016
  • Inactivation of the cytoprotective major vault protein by caspase-1 and -9
           in epithelial cells during apoptosis
    • Authors: Serena Grossi; Gabriele Fenini, Tobias Kockmann, Paulina Hennig, Michela Di Filippo, Hans-Dietmar Beer
      Abstract: Inflammasome activation induces caspase-1-dependent secretion of the proinflammatory cytokine IL-1β. In addition, caspase-1 activates gasdermin D (GSDMD) in immune cells causing pyroptosis, a lytic type of cell death. In contrast, UVB irradiation of human primary keratinocytes (HPKs) induces NLRP1 inflammasome activation, cytokines secretion and caspase-1-dependent apoptosis, rather than pyroptosis. Here, we addressed the molecular mechanisms underlying the role of caspase-1 in UVB-induced cell death of HPKs.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-23
      DOI: 10.1016/j.jid.2019.11.015
  • T-Type calcium channels as potential therapeutic targets in
           vemurafenib-resistant BRAFV600E melanoma
    • Authors: C. Barceló; P. Sisó, O. Maiques, S. García-Mulero, R. Sanz-Pamplona, R. Navaridas, C. Megino, I. Felip, I. Urdanibia, N. Eritja, X. Soria, J.M. Piulats, R.M. Penin, X. Dolcet, X. Matías-Guiu, R.M. Martí, A. Macià
      Abstract: Melanoma is a malignant neoplasia that is highly resistant to chemotherapy and radiotherapy and is associated with poor prognosis in advanced stage. Targeting melanoma that harbors the common BRAFV600E mutation with kinase inhibitors, such as vemurafenib, reduces tumor burden, but these tumors frequently acquire resistance to these drugs. We previously proposed that T-type calcium channel (TTCC) expression may serve as a biomarker for melanoma progression and prognosis, and we showed that TTCC blockers reduce migration and invasion rates due to autophagy blockade only in BRAFV600E-mutant melanoma cells.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-23
      DOI: 10.1016/j.jid.2019.11.014
  • NKG2D defines a subset of skin effector memory CD8 T cells with
           pro-inflammatory functions in vitiligo
    • Authors: Clément Jacquemin; Christina Martins, Fabienne Lucchese, Denis Thiolat, Alain Taieb, Julien Seneschal, Katia Boniface
      Abstract: Vitiligo is an autoimmune disease that results from the loss of melanocytes, associated with skin infiltration of CD8+ effector memory T (TEM) cells with a Tc1 skewed immune response. Natural killer group 2D (NKG2D) is an activating receptor found on immune cells, in particular NK and activated CD8+ T cells, that is able to produce a high amount of IFN-γ. Here we found that NKG2D expression was increased in vitiligo skin CD8+ TEM cells and was promoted by IL-15. Phenotypic and functional analyses showed that NKG2D+ CD8+ skin TEM cells displayed an activated phenotype and produced elevated levels of both IFN-γ and TNF-α.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-23
      DOI: 10.1016/j.jid.2019.11.013
  • Tussilagonone ameliorates psoriatic features in keratinocytes and
           imiquimod-induced psoriasis-like lesions in mice via Nrf2 activation
    • Authors: Joohee Lee; Kwangho Song, Paul Hiebert, Sabine Werner, Tae-Gyun Kim, Yeong Shik Kim
      Abstract: Psoriasis is a common inflammatory skin disorder which is characterized by keratinocyte hyperproliferation and abnormal differentiation, resulting in the thickening of the epidermis and stratum corneum. In the present study, we investigated in vitro and in vivo pharmacological effects of tussilagonone (TGN), a sesquiterpenoid isolated from Tussilago farfara, on transcription factors relevant for the pathogenesis of psoriasis. TGN inhibited activation of NF-kB and STAT3, leading to the attenuated expression of psoriasis-related inflammatory genes and suppression of keratinocytes hyperproliferation.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-23
      DOI: 10.1016/j.jid.2019.12.008
  • The Interaction of LILRB2 with HLA-B is Associated with Psoriasis
    • Authors: Rebecca L. Yanovsky; Haoyan Chen, Stephen Leslie, Mary Carrington, Wilson Liao
      Abstract: The strongest signal for genetic susceptibility to psoriasis resides within the major histocompatibility complex (MHC) near class I loci (Okada et al., 2014). However, the mechanistic basis for how MHC associations confer psoriasis risk has yet to be fully elucidated (Prinz, 2018). Fine-mapping studies have identified specific amino acids in the peptide binding groove of HLA-B and HLA-C as conferring risk (Chen et al., 2012, Okada et al., 2014). This suggests that psoriasis risk may be mediated through HLA presentation of autoantigens.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-21
      DOI: 10.1016/j.jid.2019.12.006
  • Using Implementation Science to Optimize the Uptake of Evidence-Based
           Medicine into Dermatology Practice
    • Authors: Sepideh Ashrafzadeh; Joshua P. Metlay, Niteesh K. Choudhry, Karen M. Emmons, Maryam M. Asgari
      Abstract: An estimated 17-year lag exists between evidence generation and its integration into routine clinical care. The field of implementation science has emerged to close this gap by applying rigorous methods to systematically study the obstacles and facilitators of the uptake of evidence-based practices. However, implementation science has not gained wide traction in dermatology. In this narrative review, we use literature and expert input to introduce implementation science and key frameworks for implementing interventions and evaluating their uptake.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-19
  • Staphylococcus aureus skin colonization is enhanced by the interaction of
           neutrophil extracellular traps with keratinocytes
    • Authors: Katharina Bitschar; Lena Staudenmaier, Laura Klink, Jule Focken, Birgit Sauer, Birgit Fehrenbacher, Franziska Herster, Zsofia Bittner, Lisa Bleul, Martin Schaller, Christiane Wolz, Alexander N.R. Weber, Andreas Peschel, Birgit Schittek
      Abstract: Staphylococcus aureus is a facultative pathogen found on skin and nasal surfaces. It is usually absent from the skin of healthy humans but frequently colonizes the skin of atopic dermatitis patients.Here we investigate the functional role of neutrophils in the initial steps of S. aureus skin colonization and how skin commensals modulate the S. aureus-induced recruitment of neutrophils to the skin. By using an epicutaneous mouse skin colonization model we show that skin inflammation induced by tape-stripping leads to a rapid recruitment of neutrophils which correlates with enhanced S.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-17
  • GNA11 mutation as a cause of Sturge Weber Syndrome - expansion of the
           phenotypic spectrum of G-protein related mosaicism and the associated
           clinical diagnoses
    • Authors: Satyamaanasa Polubothu; Lara A-Olabi, Maria Carmen del Boente, Alisha Chacko, Georgios Eleftheriou, Mary Glover, David Jiménez-Gallo, Elizabeth A. Jones, Debra Lomas, Regina Fölster-Holst, Samira Syed, Monika Tasani, Anna Thomas, Martin Tisdall, Antonio Torrelo, Sarah Aylett, Veronica A. Kinsler
      Abstract: GNA11 and GNAQ are highly homologous genes encoding different Gα subunits of the Gαq subfamily of heterotrimeric G-proteins. GNAQ mutation mosaicism has previously been found to cause Sturge-Weber syndrome (SWS) and isolated capillary malformations(Shirley et al., 2013). We recently described post-zygotic activating mutations in GNA11 or GNAQ as causes of Phakomatosis pigmentovascularis (PPV)(Thomas et al., 2016), a group of conditions defined by the presence of both pigmentary and vascular birthmarks(Happle, 2005, Ota, 1947), and GNAQ mosaicism as a cause of Extensive or atypical dermal melanocytosis (EDM)(Thomas et al., 2016).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-12
  • Utilizing Machine Learning for Image Quality Assessment for Reflectance
           Confocal Microscopy
    • Authors: Kivanc Kose; Alican Bozkurt, Christi Alessi Fox, Dana H. Brooks, Jennifer G. Dy, Milind Rajadhyaksha, Melissa Gill
      Abstract: In vivo reflectance confocal microscopy (RCM) enables clinicians to examine lesions’ morphological and cytological information in epidermal and dermal layers, while reducing the need for biopsies. As RCM is being adopted more widely, the workflow is expanding from real-time diagnosis at the bedside to include a “capture, store and forward” model with image interpretation and diagnosis occurring offsite, similar to radiology. As the patient may no longer be present at the time of image interpretation, quality assurance is key during image acquisition.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-12
  • Predictive metagenomic analysis reveals a role of cutaneous dysbiosis in
           the development of hidradenitis suppurativa
    • Authors: Hans Christian Ring; Jonathan Thorsen, Astrid Helene Jørgensen, Lene Bay, Thomas Bjarnsholt, Kurt Fuursted, Simon Francis Thomsen, Gregor Borut Jemec
      Abstract: we read with great interest the recent published manuscript by Schneider AM et al.(Schneider et al., 2019). The authors investigated the bacterial microbiome in patients with hidradenitis suppurativa (HS) and healthy controls using Next-Generation Sequencing (NGS) of 16S rRNA marker genes. Overall, the authors demonstrated several factors that point to a potential involvement of the microbiome in the pathogenesis of HS. Indeed, the authors further add to the hypothesis that the reduced presence of sebaceous glands and the subsequent reduced presence of Propionibacteria spp.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-12
      DOI: 10.1016/j.jid.2019.11.011
  • Loss of the Epigenetic Mark, 5-hmC, in Psoriasis: Implications for
           Epidermal Stem Cell Dysregulation
    • Authors: Feng Li; Christine W. Yuan, Shuyun Xu, Tingjian Zu, Yvon Woappi, Catherine A.A. Lee, Phammela Abarzua, Michael Wells, Matthew R. Ramsey, Natasha Y. Frank, Xunwei Wu, Anna Mandinova, Markus H. Frank, Christine G. Lian, George F. Murphy
      Abstract: Epigenetic regulation has profound influence on stem cell fate during normal development in maintenance of physiologic tissue homeostasis. Here we report diminished ten-eleven translocation (TET) methylcytosine dioxygenase expression and loss of the DNA hydroxymethylation mark, 5-hydroxymethylcytosine (5-hmC), in keratinocyte stem cells (KSCs) and transit-amplifying cells (TACs) in human psoriasis and in imiquimod-induced murine psoriasis. Loss of 5-hmC was associated with dysregulated KSC kinetics, resulting in accumulation of nestin and FABP5-expressing TACs to produce classic psoriatic epidermal architecture.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-11
  • The transcription factor Foxn1 regulates skin adipogenesis and affects
           susceptibility to diet-induced obesity
    • Authors: Katarzyna Walendzik; Marta Kopcewicz, Joanna Bukowska, Grzegorz Panasiewicz, Bozena Szafranska, Barbara Gawronska-Kozak
      Abstract: Foxn1, a transcription factor expressed in the epidermis, regulates keratinocyte differentiation and participates in skin wound healing. In the present study, we explored the impact of Foxn1 insufficiency on diet-stimulated weight gain and dermal white adipose tissue regulation in the intact and wounded skin of Foxn1eGFP/+ (heterozygotes, Foxn1 insufficient) mice in the context of age and diet. The results showed that on a high-fat diet, Foxn1eGFP/+ mice gained significantly less body weight than their Foxn1+/+ counterparts (Foxn1-sufficient mice).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-04
      DOI: 10.1016/j.jid.2019.11.010
  • The Utility of T-Cell Clonality in Differential Diagnostics of Acute
           Graft-vs-Host Disease from Drug Hypersensitivity Reaction
    • Authors: Li-Wei Chang; Linda T. Doan, Paul Fields, Marissa Vignali, Oleg E. Akilov
      Abstract: Graft-versus-host disease (GVHD) is a severe complication of hematopoietic stem cell transplantation (HSCT). The skin involvement often appears prior to the involvement of other organs. Cutaneous manifestations of acute GVHD have features that are similar both clinically and histologically to other morbilliform eruptions, such as drug hypersensitivity reaction (DHR) and viral or bacterial exanthem; thus, creating a diagnostic pitfall. The correct diagnosis of DHR vs. GVHD is crucial since the therapy of those two conditions has a different direction: discontinuation of the offending agent in DHR and early administration of a high dose of systemic steroids in GVHD.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-02
      DOI: 10.1016/j.jid.2019.11.009
  • Homozygous nonsense mutation in DSC3 resulting in skin fragility and
    • Authors: Alexandros Onoufriadis; Noha Ahmed, Hagar Besser, Alyson Guy, Lu Liu, Alexandros Marantzidis, Evangelia Kesidou, Maria Papanikolaou, Michael A. Simpson, Jemima E. Mellerio, John Y.W. Lee, John A. McGrath
      Abstract: To the Editor
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-29
  • Hereditary mucoepithelial dysplasia results from heterozygous variants at
           p.Arg557 mutational hotspot in SREBF1, encoding a transcription factor
           involved in cholesterol homeostasis
    • Authors: Fanny Morice-Picard; Vincent Michaud, Eulalie Lasseaux, Hamid Reza Rezvani, Claudio Plaisant, Didier Bessis, Christine Leauté-Labrèze, Benoit Arveiler, Alain Taieb, Aurélien Trimouille, Franck Boralevi
      Abstract: To the editor
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-29
  • High levels of platelet-lymphocyte complexes in psoriasis patients are
           associated with a better response to anti-TNF-α therapy
    • Authors: María Teresa Sanz-Martínez; Esther Moga Naranjo, Miguel Angel Sánchez Martínez, Carlos Zamora Atenza, Silvia Vidal Alcorisa, Cándido Juárez Rubio, Lluís Puig
      Abstract: Psoriasis is currently considered to be an immune-mediated disease whose patho-mechanisms involve platelet activation, which seems to correlate with activity disease. Platelet activation is associated with the formation of platelet-lymphocyte complexes, though their significance remains unknown. Moreover, biological treatments targeting TNF-α reduce platelet activation.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-25
      DOI: 10.1016/j.jid.2019.08.457
  • Polyomavirus-positive Merkel cell carcinoma derived from a trichoblastoma
           suggests an epithelial origin of this Merkel cell carcinoma
    • Authors: Thibault Kervarrec; Mohanad Aljundi, Silke Appenzeller, Mahtab Samimi, Eve Maubec, Bernard Cribier, Lydia Deschamps, Bhavishya Sarma, Eva-Maria Sarosi, Patricia Berthon, Annie Levy, Guilhem Bousquet, Anne Tallet, Antoine Touzé, Serge Guyétant, David Schrama, Roland Houben
      Abstract: Merkel cell carcinoma (MCC), an aggressive neuroendocrine carcinoma of the skin, is to date the only human cancer known to be frequently caused by a polyomavirus. However, it is a matter of debate which cells are targeted by the Merkel cell polyomavirus (MCPyV) to give rise to the phenotypically multifaceted MCC cells.To assess the lineage of origin of MCPyV-positive MCC, genetic analysis of a very rare tumor combining benign trichoblastoma and MCPyV-positive MCC was conducted by massive parallel sequencing.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-21
      DOI: 10.1016/j.jid.2019.09.026
  • Overexpression of MYB in the skin induces alopecia and epidermal
    • Authors: Yuan Hu; Zhongya Song, Jiang Chen, Carlos Caulin
      Abstract: The skin homeostasis is controlled by a complex interplay between tightly regulated transcription factors and signaling pathways. MYB is a transcription factor expressed in hair follicle progenitor cells and found overexpressed in adnexal skin tumors. However, the biological consequences of deregulated MYB expression in the skin remain poorly understood. To address this, we generated transgenic mice that overexpress MYB in epidermal and follicular keratinocytes. These mice exhibited a normal hair coat after birth, but gradually developed alopecia, accompanied by altered follicular differentiation, disrupted hair cycle and a marked depletion of hair follicle stem cells.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-20
  • Interaction of Resistin and Systolic Blood Pressure in Psoriasis Severity
    • Authors: Divya Seth; Alexa N. Ehlert, Jackelyn B. Golden, Giovanni Damiani, Thomas S. McCormick, Mark J. Cameron, Kevin D. Cooper
      Abstract: To the Editor, in a prospective cohort study, Snekvik et al. (2017) observed that obesity doubles the incidence risk for psoriasis. This finding may be attributable to the inflammatory role of adipokines: adipose-tissue associated hormones including resistin, leptin, adiponectin, and others. Resistin induces inflammatory markers, including TNF-alpha and IL-6 (Johnston et al. 2008). Independent associations have been reported between psoriasis, elevated serum resistin levels, and cardiovascular disease (CVD) (Muse et al.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-14
      DOI: 10.1016/j.jid.2019.07.727
  • Adenosine Promotes Human Hair Growth And Inhibits Catagen Transition In
           Vitro – Role Of The Outer Root Sheath Keratinocytes
    • Authors: Erika Lisztes; Balázs István Tóth, Marta Bertolini, Imre Lőrinc Szabó, Nóra Zákány, Attila Oláh, Attila Gábor Szöllősi, Ralf Paus, Tamás Bíró
      Abstract: Adenosine is a locally produced mediator exerting several cytoprotective effects via G-protein coupled cell membrane adenosine receptors (ARs) (Linden 2005). In the skin, adenosine can influence several (patho)physiological processes, such as wound healing, development of scleroderma, cutaneous inflammation, allergic reactions or barrier formation (Andrés et al. 2017; Burnstock et al. 2012; Silva-Vilches et al. 2019). A beneficial effect of adenosine on hair growth has already been reported in clinical studies: topical adenosine treatment was shown to alleviate the symptoms of alopecia by increasing hair thickness and promoting anagen hair growth (Iwabuchi et al.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-12
      DOI: 10.1016/j.jid.2019.08.456
  • Reverse phenotyping in patients with skin capillary malformations and
           mosaic GNAQ or GNA11 mutations defines a clinical spectrum with
           genotype-phenotype correlation
    • Authors: Maud Jordan; Virginie Carmignac, Arthur Sorlin, Paul Kuentz, Juliette Albuisson, Luca Borradori, Emmanuelle Bourrat, Odile Boute, Nenad Bukvic, Anne-Claire Bursztejn, Christine Chiaverini, Bruno Delobel, Marine Fournet, Jehanne Martel, Alice Goldenberg, Smaïl Hadj-Rabia, Antoine Mahé, Annabel Maruani, Juliette Mazereeuw, Cyril Mignot, Fanny Morice-Picard, Marie-Laure Moutard, Florence Petit, Justine Pasteur, Alice Phan, Sandra Whalen, Marjolaine Willems, Christophe Philippe, Pierre Vabres
      Abstract: Post-zygotic mutations in GNAQ/GNA11 genes encoding heterotrimeric G protein alpha subunits account for skin mosaic conditions with vascular or pigmentary anomalies (Shirley et al. 2013; Thomas et al. 2016; Couto et al. 2017; Siegel et al. 2018). We sought to delineate the phenotype of 32 patients with skin capillary malformations (CMs) harbouring an activating post-zygotic mutation in GNA11 or GNAQ in affected skin. Nevus flammeus, ipsilateral segmental overgrowth, varicose veins and macrocephaly were associated with GNAQ mutations, whereas cutis marmorata, nevus anemicus, and ipsilateral hypotrophy were associated with GNA11 mutations.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-11
      DOI: 10.1016/j.jid.2019.08.455
  • Persistence of inflammatory phenotype in residual psoriatic plaques in
           patients on effective biologic therapy
    • Authors: Shunya Mashiko; Rebecca M. Edelmayer, Yingtao Bi, Lauren M. Olson, Joseph B. Wetter, Jing Wang, Catherine Maari, Etienne Saint-Cyr Proulx, Vivek Kaimal, Xuan Li, Katherine Salte, Sandra Garcet, Arun K. Kannan, Susan M. Huang, Xiaohong Cao, Zheng Liu, James G. Krueger, Marika Sarfati, Robert Bissonnette, Kathleen M. Smith
      Abstract: Many psoriasis patients treated with biologics do not achieve total skin clearance. These patients possess “residual plaques” despite ongoing biologic treatment. To elucidate mechanisms of plaque persistence despite overall good drug response, we studied fifty subjects: psoriasis patients with residual plaques treated with one of three different biologics, untreated patients, and healthy controls. Skin biopsies from all subjects were characterized using three methods: mRNA expression, histology, and FACS of skin hematopoietic cells.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-09
      DOI: 10.1016/j.jid.2019.09.027
  • Activation of GPCR-Gαi signaling increases keratinocyte proliferation and
           reduces differentiation, leading to epidermal hyperplasia
    • Authors: M. Pilar Pedro; Natalia Salinas Parra, J. Silvio Gutkind, Ramiro Iglesias-Bartolome
      Abstract: G-protein-coupled receptors (GPCRs) and their associated heterotrimeric G proteins impinge on pathways that control epithelial cell self-renewal and differentiation. While it is known that Gαs signaling regulates skin homeostasis in vivo, the role of GPCR-coupled Gαi proteins in the skin is unclear. Here, by using a chemogenetic approach, we demonstrate that GPCR-Gαi activation can regulate keratinocyte proliferation and differentiation and that overactivation of Gαi-signaling in the basal compartment of the mouse skin can lead to epidermal hyperplasia.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-07
  • E2F1/IGF-1R loop contributes to BRAF inhibitor resistance in melanoma
    • Authors: Xiao Liu; Jun Mi, Haihong Qin, Zheng Li, Jingxiu Chai, Ming Li, Jinfeng Wu, Jinhua Xu
      Abstract: TO THE EDITOR
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-06
      DOI: 10.1016/j.jid.2019.09.025
  • The Identification of Potential Therapeutic Targets for Cutaneous Squamous
           Cell Carcinoma
    • Authors: Angela McHugh; Kenneth Fernandes, Nerime Chinner, Adel F.M. Ibrahim, Amit K. Garg, Garry Boag, Lydia A. Hepburn, Charlotte M. Proby, Irene M. Leigh, Mark K. Saville
      Abstract: We carried out an siRNA screen to identify targets for cutaneous squamous cell carcinoma (cSCC) therapy in the ubiquitin/ubiquitin-like (UBL) system. We provide evidence for selective anti-cSCC activity of knockdown of the E3 ubiquitin ligase MARCH4, the ATPase p97/VCP, the deubiquitinating enzyme USP8, the cullin-RING ligase (CRL) 4 substrate receptor CDT2/DTL and components of the anaphase promoting complex/cyclosome (APC/C). Specifically attenuating CRL4CDT2 by CDT2 knockdown can be more potent in killing cSCC cells than targeting CRLs or CRL4s in general by RBX1 or DDB1 depletion.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-06
      DOI: 10.1016/j.jid.2019.09.024
  • Early quantification of systemic inflammatory-proteins predicts long-term
           treatment response to Tofacitinib and Etanercept
    • Authors: Lewis E. Tomalin; Jaehwan Kim, Joel Correa da Rosa, Julie Lee, Lori J. Fitz, Gabriel Berstein, Hernan Valdez, Robert Wolk, James G. Krueger, Mayte Suárez-Fariñas
      Abstract: The application of machine-learning to longitudinal gene-expression profiles has demonstrated potential to decrease the “assessment gap”, between biochemical determination and clinical manifestation, of a patient’s response to treatment. Although Psoriasis is a proven testing ground for treatment-response prediction using transcriptomic data from clinically accessible skin-biopsies, these biopsies are expensive, invasive and challenging to obtain from certain body areas. Response prediction from blood biochemical measurements could be a cheaper, less invasive predictive platform.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-06
      DOI: 10.1016/j.jid.2019.09.023
    • Authors: Ming Yang Lee; Hong-Zhan Wang, Thomas W. White, Tony Brooks, Alan Pittman, Heerni Halai, Anastasia Petrova, Diane Xu, Stephen L. Hart, Veronica A. Kinsler, Wei-Li Di
      Abstract: Keratitis-ichthyosis-deafness (KID) syndrome is a severe, untreatable condition characterized by ocular, auditory and cutaneous abnormalities, with major complications of infection and skin cancer. 86% of cases are caused by a heterozygous missense mutation (c.148G>A, p.D50N) in the GJB2 gene, encoding gap junction protein connexin 26 (Cx26), which alters gating properties of Cx26 channels in a dominant manner. We hypothesized that a mutant-allele-specific siRNA (AS-siRNA) could rescue the cellular phenotype in patient keratinocytes.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-06
      DOI: 10.1016/j.jid.2019.09.022
  • Alterations of Immune and Keratinization Gene Expression in Papulopustular
           Rosacea by Whole Transcriptome Analysis
    • Authors: Yi-Hsien Shih; Jin Xu, Anusha Kumar, Rui Li, Anne Lynn S. Chang
      Abstract: Papulopustular rosacea (PPR) is a chronic, incurable disease with limited systemic treatment options (Holmes et al., 2018, van Zuuren and Fedorowicz, 2016). Expanding knowledge of the molecular underpinnings provides future directions for investigation to better combat PPR.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-06
      DOI: 10.1016/j.jid.2019.09.021
  • Enrichment of polyfunctional IL-17 producing T cells in paradoxical
           psoriasis skin lesions
    • Authors: Barry Moran; Catriona Gallagher, Anne Marie Tobin, Jean M. Fletcher
      Abstract: Despite anti-TNF therapies’ effectiveness in treating inflammatory diseases such as psoriasis, inflammatory bowel disease and inflammatory arthritis (Toussirot and Aubin, 2016), there is a small cohort that upon treatment, develop psoriasis-like lesions, termed paradoxical, or reactive, psoriasis. Although paradoxical psoriasis can often be treated topically, discontinuation of the anti-TNF therapy is necessary in approximately one third of cases. The incidence of anti-TNF induced paradoxical psoriasis was reported to be 1.7% (Guerra et al., 2016), and the number of cases is likely to rise in parallel with the increasing use of biologics.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-01
  • Sex-stratified polygenic risk score identifies individuals at increased
           risk of basal cell carcinoma
    • Authors: Michelle R. Roberts; Joanne E. Sordillo, Peter Kraft, Maryam M. Asgari
      Abstract: The incidence of basal cell carcinoma (BCC) is higher among men than women. Susceptibility loci for BCC have been identified through genome-wide association studies (GWAS), and two previous studies have found polygenic risk scores (PRS) to be significantly associated with risk of BCC. However, to our knowledge, sex-stratified PRS analyses examining the genetic contribution to BCC risk among men and women have not been previously reported. To quantify the contribution of genetic variability on BCC risk by sex, we derived a polygenic risk score and estimated the genetic relative risk distribution for men and women.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-01
      DOI: 10.1016/j.jid.2019.09.020
  • Preclinical Evidence for Targeting PI3K/mTOR Signaling with
           Dual-Inhibitors as a New Therapeutic Strategy against Cutaneous T Cell
    • Authors: Antonella Bresin; Cristina Cristofoletti, Elisabetta Caprini, Maria Cantonetti, Alessandro Monopoli, Giandomenico Russo, Maria Grazia Narducci.
      Abstract: The PI3K/AKT/mTOR pathway is hyperactivated in many tumors, as well as in cutaneous T-cell lymphoma (CTCL) which includes mycosis fungoides (MF) and the aggressive variant known as Sezary syndrome (SS). TORC1 signaling is activated in SS cells by cytokines and chemokines, which are overexpressed in SS tissues. Furthermore, the recurrent copy number variation (CNV) of genes belonging to this cascade, such as PTEN, LKB1, and P70S6K, contributes to the hyperactivation of the pathway. The aim of this study was to investigate the therapeutic potential of mTOR inhibitors in CTCL.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-01
      DOI: 10.1016/j.jid.2019.08.454
  • A TP63 mutation causes prominent alopecia with mild ectodermal dysplasia
    • Authors: Sabine Duchatelet; Claudia Russo, Christian Osterburg, Stéphanie Mallet, Christine Bole-Feysot, Patrick Nitschké, Marie-Aleth Richard, Volker Dötsch, Caterina Missero, Aude Nassif, Alain Hovnanian
      Abstract: TP63 mutations underlie several autosomal dominant ectodermal dysplasias (EDs) characterized by various combinations of limb, ectodermal and orofacial abnormalities (Rinne et al., 2007). We describe a family with prominent alopecia and mild ED features, which co-segregate with a TP63 mutation.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-01
      DOI: 10.1016/j.jid.2019.06.154
  • Harnessing the secretome of hair follicle fibroblasts to accelerate ex
           vivo healing of human skin wounds
    • Authors: Helena Topouzi; Colin J. Boyle, Greg Williams, Claire A. Higgins
      Abstract: In skin homeostasis, dermal fibroblasts are responsible for coordinating the migration and differentiation of overlying epithelial keratinocytes. As hairy skin heals faster than non-hairy skin, we took bio-inspiration from the follicle and hypothesised that follicular fibroblasts would accelerate skin re-epithelialisation after injury faster than interfollicular fibroblasts. Using both in vitro and ex vivo models of human skin wound closure, we found that hair follicle dermal papilla fibroblasts could accelerate closure of in vitro scratch wounds by 1.8-fold and epithelial growth capacity by 1.5-fold compared to controls (p
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-01
      DOI: 10.1016/j.jid.2019.09.019
  • Enrichment of plasma cells in the peripheral blood and skin of
           hidradenitis suppurativa patients
    • Authors: J. Musilova; B. Moran, C.M. Sweeney, A. Malara, A. Zaborowski, R. Hughes, D.C. Winter, J.M. Fletcher, B. Kirby
      Abstract: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by painful deep-seated recurrent nodules and abscesses in axillary, inguinal and perineal areas (Jemec, 2012). It is a complex disease with an aetiology including genetic variations, environmental factors and aberrant innate and adaptive immune functions (Alikhan et al., 2009, Kelly et al., 2014, Moran et al., 2017).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-11-01
      DOI: 10.1016/j.jid.2019.08.453
  • Nanoparticle-coupled topical methotrexate can normalize immune responses
           and induce tissue remodeling in psoriasis
    • Authors: Alaz Özcan; Dilara Sahin, Daniela Impellizzieri, Tuan T. Nguyen, Jürg Hafner, Nikhil Yawalkar, Dennis Kurzbach, Ge Tan, Cezmi A. Akdis, Jakob Nilsson, Onur Boyman, Antonios G.A. Kolios
      Abstract: Methotrexate (MTX) is an anti-proliferative drug used for treating inflammatory diseases including psoriasis. Nevertheless, its use in localized therapy is impeded due to poor transdermal penetration.We show that MTX coupled with gold-nanoparticles (GNPs) demonstrates superior anti-inflammatory efficacy compared to MTX-alone in an imiquimod (IMQ)-induced mouse model, significantly reducing γδ T cells, CD4+ T cells, and neutrophils. Furthermore, it was well tolerated upon systemic and topical administration.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-31
      DOI: 10.1016/j.jid.2019.09.018
  • Palmitoyl acyltransferase activity of ZDHHC13 regulates skin barrier
           development partly by controlling PADi3 and TGM1 protein stability
    • Authors: Li-Ying Chen; Kuo-Ray Lin, Yi-Ju Chen, Yun-Jung Chiang, Kun-Chin Ho, Li-Fen Shen, I-Wen Song, Kai-Ming Liu, Hsin-Fang Yang-Yen, Yu-Ju Chen, Yuan-Tsong Chen, Fu-Tong Liu, Jeffrey J.Y. Yen
      Abstract: Deficiency of the palmitoyl-acyl transferase ZDHHC13 compromises skin barrier permeability and renders mice susceptible to environmental bacterial infection and inflammatory dermatitis. It had been unclear how lack of ZDHHC13 proteins resulted in cutaneous abnormalities. In this study, we first demonstrate that enzymatic palmitoylation activity, rather than protein scaffolding, by ZDHHC13 is essential for skin barrier integrity, showing that knock-in mice bearing an enzymatically dead DQ-to-AA ZDHHC13 mutation cyclically lost their hair after weaning, recapitulating knock-out phenotypes of skin inflammation and dermatitis.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-25
      DOI: 10.1016/j.jid.2019.09.017
  • Association between human leukocyte antigen type and keratinocyte
           carcinoma risk in renal transplant recipients
    • Authors: Yuhree Kim; David Wojciechowski, Vikram Pattanayak, Hang Lee, Maryam M. Asgari
      Abstract: Keratinocyte carcinoma (KC) defined as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) is the most common malignancy among non-Hispanic white (NHW) renal transplant recipients (RTRs). While recent genome-wide association studies reported that the class II human leukocyte antigen (HLA) is associated with KC risk, epidemiologic data on HLA type and KC risk in RTRs is limited. Using an institutional cohort of NHW RTRs transplanted between 1993-2017, we examined the association between pre-transplant molecular HLA types and KC risk.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-24
      DOI: 10.1016/j.jid.2019.09.016
    • Authors: Walter Boiten; Jeroen van Smeden, Joke Bouwstra
      Abstract: The lipids covalently bound to the cornified envelope of corneocytes are essential for the human skin barrier (Swartzendruber et al., 1987). Together with the unbound lipids they form a matrix regulating the permeability for water and pathogens through the stratum corneum (SC). Three main lipid classes are observed in the SC: sterols, fatty acids, and ceramides. Bound ceramides are a subset of the unbound ceramides and have an ultra-long omega-hydroxyl chain (OCer)(Farwanah et al., 2007, Hill et al., 2006).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-17
      DOI: 10.1016/j.jid.2019.09.013
  • Development, validation and interpretation of the PROMIS Itch
           Questionnaire: a patient-reported outcome measure for the quality of life
           impact of itch
    • Authors: Jonathan I. Silverberg; Jin-Shei Lai, Robert W. Kantor, Prarthana Dalal, Catherine Hickey, Sara Shaunfield, Karen Kaiser, Helena Correia, David Cella
      Abstract: Current patient-reported outcome measures for itch are limited and may not capture its full impact on health-related quality of life (HRQOL). We sought to develop, calibrate and validate banks of questions assessing the HRQOL impact of itch as part of Patient-Reported Outcomes Measurement Information System® (PROMIS®). A systematic process of literature review, content-expert review, qualitative research, testing in a sample of 600 adults, classical test theory methods, and item response theory (IRT) analyses were applied.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-16
      DOI: 10.1016/j.jid.2019.08.452
    • Authors: Jouni Uitto; Qianjin Lu, Gang Wang
      First page: 729
      Abstract: On October 1, 2019, the Peoples Republic of China celebrated the 70th anniversary of its foundation. The country, from its humble beginnings as an impoverished nation, has experienced over the past 70 years a remarkable economic growth. Accompanying the economic growth, there has been a rapid expansion of the research enterprise in China, including dermatological and cutaneous biology research. This is reflected by the number of English language articles listed in PubMed, which increased over the past decade (2009-2019) from 147 to 1,337, as published by dermatologists in China (Figure 1a).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-17
      DOI: 10.1016/j.jid.2019.11.012
  • Migration and Function of Memory CD8+ T Cells in Skin
    • Authors: Toshiro Hirai; Sarah K. Whitley, Daniel H. Kaplan
      First page: 748
      Abstract: CD8+ memory T cells provide anamnestic host defense against intracellular pathogens and cancer immunosurveillance but are also pathogenic in some autoimmune diseases. In mouse skin, there are two unique subsets of CD8+ memory T cells, resident memory cells that reside long-term in steady state skin and recirculating memory cells that are transient. They have distinct mechanisms of recruitment, development, and maintenance in response to skin-derived signals. In this review, we will focus on these mechanisms and the functional relationship of these two types of CD8+ memory cells with host defense and disease.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-12-04
      DOI: 10.1016/j.jid.2019.09.014
  • Defining transcriptional signatures of human hair follicle cell states
    • Authors: R. Takahashi; A. Grzenda, T. Allison, J. Rawnsley, S.J. Balin, S. Sabri, K. Plath, W.E. Lowry
      First page: 764
      Abstract: The epidermis and its appendage, the hair follicle, represent an elegant developmental system in which cells are replenished with regularity because of controlled proliferation, lineage specification, and terminal differentiation. While transcriptome data exists for human epidermal and dermal cells, the hair follicle remains poorly characterized. Through single-cell resolution profiling of the epidermis and anagen hair follicle, we characterized the anatomical, transcriptional, functional, and pathological profiles of distinct epidermal, hair follicle, and hair follicle-associated cell subpopulations including melanocytes, endothelial cells, and immune cells.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-30
      DOI: 10.1016/j.jid.2019.07.726
  • Kallikrein-mediated cytokeratin 10 degradation is required for VZV
           propagation in skin
    • Authors: C. Tommasi; C. Rogerson, D.P. Depledge, M. Jones, A.S. Naeem, C. Venturini, D. Frampton, H.J. Tutill, B. Way, J. Breuer, R.F.L. O’Shaughnessy
      First page: 774
      Abstract: Varicella Zoster Virus (VZV) is a skin-tropic virus that infects epidermal keratinocytes and causes chickenpox. Although common, VZV infection can be life-threatening particularly in the immunocompromised. Therefore, understanding VZV-keratinocyte interactions is important to find new treatments beyond vaccination and anti-viral drugs. In VZV- infected skin, Kallikrein 6 (KLK6), and the ubiquitin-ligase MDM2 are up-regulated concomitant with Keratin 10 (K10) down-regulation. MDM2 binds to K10 targeting it for degradation via the ubiquitin-proteasome pathway.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-15
      DOI: 10.1016/j.jid.2019.08.448
  • Interpretability of the Quality Of Life in Hand Eczema Questionnaire
    • Authors: Jart A.F. Oosterhaven; Robert F. Ofenloch, Marie L.A. Schuttelaar
      First page: 785
      Abstract: The Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) is used to measure impairment of health-related quality of life (HRQoL) in hand eczema. Here, we prospectively studied the interpretability of international QOLHEQ scores at three time points: baseline, after 1-3 days (T1) and after 4-12 weeks (T2). Adult patients with hand eczema completed the QOLHEQ and anchor questions for overall assessment of HRQoL impairment. Interpretability of single scores was assessed at baseline by defining severity bands based on agreement with the anchor questions.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-10
      DOI: 10.1016/j.jid.2019.08.450
  • Somatic mosaic NLRP3 mutations and inflammasome activation in late-onset
           chronic urticaria
    • Authors: Eman Assrawi; Camille Louvrier, Clémence Lepelletier, Sophie Georgin-Lavialle, Jean-David Bouaziz, Fawaz Awad, Florence Moinet, Philippe Moguelet, Marie Dominique Vignon-Pennamen, William Piterboth, Claire Jumeau, Laetitia Cobret, Elma ElKhouri, Bruno Copin, Philippe Duquesnoy, Marie Legendre, Gilles Grateau, Sonia A. Karabina, Serge Amselem, Irina Giurgea
      First page: 791
      Abstract: Chronic urticaria is a common skin disorder with heterogeneous causes. In the absence of physical triggers, chronic urticarial rash is called idiopathic or spontaneous. The objective of the current study was to identify the molecular and cellular bases of a disease condition displayed by two unrelated patients aged over 60 years who presented for two decades with a chronic urticaria resistant to standard therapy which occurred in the context of systemic inflammation not triggered by cold. In both patients, a targeted sequencing approach using a next generation technology identified somatic mosaic mutations in NLRP3, a gene encoding a key inflammasome component.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-09-09
      DOI: 10.1016/j.jid.2019.06.153
  • Exome-wide rare loss-of-function variant enrichment study of 21,347 Han
           Chinese individuals identifies four susceptibility genes for psoriasis
    • Authors: Chao Yang; Mengyun Chen, He Huang, Xueying Li, Danfeng Qian, Xiaojie Hong, Lijun Zheng, Jiaqi Hong, Jiaqi Hong, Zhengwei Zhu, Xiaodong Zheng, Yujun Sheng, Xuejun Zhang
      First page: 799
      Abstract: Most psoriasis-related genes or loci identified by genome-wide association studies (GWASs) represent common clusters and are located in noncoding regions of the human genome, providing only limited evidence for the roles of rare coding variants in psoriasis. Two exome-wide case-control genotyping data sets (11,245 cases and 11,177 controls) were obtained from our previous study. Quality controls were established for each data set, and the markers remaining in each set were annotated using ANNOVAR.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-07-31
      DOI: 10.1016/j.jid.2019.07.692
  • Pathogenic CD8+ epidermis-resident memory T cells displace dendritic
           epidermal T cells in allergic dermatitis
    • Authors: Anne-Sofie Ø. Gadsbøll; Mia H. Jee, Anders B. Funch, Maria Alhede, Veronika Mraz, Julie F. Weber, Lauren A. Callender, Elizabeth C. Carroll, Thomas Bjarnsholt, Anders Woetmann, Niels Ødum, Allan R. Thomsen, Jeanne D. Johansen, Sian M. Henson, Carsten Geisler, Charlotte M. Bonefeld
      First page: 806
      Abstract: The skin is our interface with the outside world and consequently it is exposed to a wide range of microbes and allergens. Recent studies have indicated that allergen-specific skin-resident memory T (TRM) cells play a role in allergic contact dermatitis (ACD). However, the composition and dynamics of the epidermal T cell subsets during ACD are not known. Here we show that exposure of the skin to the experimental contact allergen 1-fluoro-2,4-dinitrobenzene (DNFB) results in a displacement of the normally occurring dendritic epidermal T cells (DETC) concomitant with an accumulation of epidermal CD8+CD69+CD103+ TRM cells in mice.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-09-10
      DOI: 10.1016/j.jid.2019.07.722
  • Interleukin-36 promotes systemic Type-I IFN responses in severe forms of
    • Authors: Marika Catapano; Marta Vergnano, Marco Romano, Satveer K. Mahil, Siew-Eng Choon, A David Burden, Helen S. Young, Ian M. Carr, Helen J. Lachmann, Giovanna Lombardi, Catherine H. Smith, Francesca D. Ciccarelli, Jonathan N. Barker, Francesca Capon
      First page: 816
      Abstract: Psoriasis is an immune-mediated skin disorder associated with severe systemic co-morbidities. While IL-36 is a key disease driver, the pathogenic role of this cytokine has mainly been investigated in skin. Thus, its effects on systemic immunity and extra-cutaneous disease manifestations remain poorly understood.To address this issue, we investigated the consequences of excessive IL-36 activity in circulating immune cells. We initially focused our attention on generalised pustular psoriasis (GPP), a clinical variant associated with pervasive up-regulation of IL-36 signalling.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-09-17
      DOI: 10.1016/j.jid.2019.08.444
  • IL-17A-producing innate lymphoid cells promote skin inflammation by
           inducing IL-33- driven type 2 immune responses
    • Authors: Minho Kim; Seon-Pil Jin, Sunhyae Jang, Ji-Yeob Choi, Doo Hyun Chung, Dong Hun Lee, Kyu Han Kim, Hye Young Kim
      First page: 827
      Abstract: Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease characterized by a type 2 cytokines secreted by T helper 2 (Th2) cells and group 2 innate lymphoid cells (ILC2s). Despite a high degree of heterogeneity, AD is still explained by type 2 immunity, and the role of interleukin (IL)-17A, which is increased in acute, pediatric, or Asian patients with AD, remains poorly understood. Here, we aimed to investigate the role of IL-17A-producing ILC3s, which are unexplored immune cells, in the pathogenesis of AD.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-16
      DOI: 10.1016/j.jid.2019.08.447
  • Homeostatic Function of Dermokine in the Skin Barrier and Inflammation
    • Authors: Akira Utsunomiya; Takenao Chino, Natsuko Utsunomiya, Vu Huy Luong, Atsushi Tokuriki, Tatsuro Naganuma, Makoto Arita, Kiyoshi Higashi, Koichi Saito, Noriyuki Suzuki, Ayako Ohara, Manabu Sugai, Koji Sugawara, Daisuke Tsuruta, Noritaka Oyama, Minoru Hasegawa
      First page: 838
      Abstract: Dermokine is a chiefly skin-specific secreted glycoprotein localized in the upper epidermis and its family consists of three splice variants in mice and five in humans. To investigate the pathophysiological impact of dermokine, we generated mice deficient for two (βγ) or all dermokine isoforms (αβγ). Both variants, especially dermokine αβγ-deficient mice exhibited scale and wrinkle formation resembling ichthyosis accompanied by transepidermal water imbalance at the neonatal stage. When reared under low humidity several dermokine αβγ-deficient mice died by postnatal day 21.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-25
      DOI: 10.1016/j.jid.2019.09.011
  • Mechanisms of itch in stasis dermatitis: Significant role of IL-31 from
    • Authors: Takashi Hashimoto; Christina Dorothy Kursewicz, Rachel Alison Fayne, Sonali Nanda, Serena Maya Shah, Leigh Nattkemper, Hiroo Yokozeki, Gil Yosipovitch
      First page: 850
      Abstract: Stasis dermatitis (SD) is a common disease in the elderly population, with pruritus being one of the bothersome symptoms. However, there are few therapeutic modalities available for SD-associated itch because little is known about its pathophysiological mechanism. Therefore, we sought to investigate the mediators of itch in SD using an immunofluorescence study on patient lesions focusing on IL-31. Ex vivo stimulation studies using murine peritoneal macrophages were also used to elucidate the pathological mechanisms of IL-31 generation.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-15
      DOI: 10.1016/j.jid.2019.09.012
  • YKL-40 promotes proliferation of CTCL tumor cells through extracellular
           signal-regulated kinase pathways
    • Authors: Hideko Suzuki; Hikari Boki, Hiroaki Kamijo, Rina Nakajima, Tomonori Oka, Naomi Shishido-Takahashi, Hiraku Suga, Makoto Sugaya, Shinichi Sato, Tomomitsu Miyagaki
      First page: 860
      Abstract: YKL-40, one of the chitinase-like proteins, is associated with the pathogenesis of wide variety of human diseases through modulation of inflammation and tissue remodeling by its diverse roles in cell proliferation, differentiation, and survival. Emerging evidence shows that aberrantly expressed YKL-40 promotes the development of malignancies by inducing proliferation of tumor cells, cytokine production, and angiogenesis by acting on various stromal cells, immune cells, and tumor cells. In this study, we investigated the expression and function of YKL-40 in cutaneous T-cell lymphoma (CTCL).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-14
      DOI: 10.1016/j.jid.2019.09.007
  • A distinct pre-treatment immune gene signature in lentigo maligna is
           associated with imiquimod response
    • Authors: Heloise Halse; Franco Caramia, Catriona A. McLean, Minyu Wang, Han Xian Aw Yeang, Simon P. Keam, Andreas Behren, Lena Ly, Martin Haskett, Jonathan Cebon, Grant A. McArthur, Paul J. Neeson, Victoria J. Mar
      First page: 869
      Abstract: Lentigo Maligna (LM) is a common subtype of in-situ melanoma on chronically sun-exposed skin, particularly the head and neck of older patients. Whilst surgery is the standard treatment, there is associated morbidity and options such as imiquimod cream or radiotherapy may be used if surgery is refused or inappropriate. Complete response rates following imiquimod treatment are variable in the literature. The aim of this study was to evaluate the host immune response both prior to and following treatment with imiquimod to better identify likely responders.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-09-30
      DOI: 10.1016/j.jid.2019.07.725
  • Inhibition of p38/MK2 signaling prevents vascular invasion of melanoma
    • Authors: Judith Wenzina; Silvio Holzner, Emmi Puujalka, Phil F. Cheng, Agnes Forsthuber, Karin Neumüller, Klaudia Schossleitner, Beate M. Lichtenberger, Mitchell P. Levesque, Peter Petzelbauer
      First page: 878
      Abstract: Melanoma cells can switch between distinct gene expression profiles, resulting in “proliferative” and “invasive” phenotypes. Signaling pathways involved in this switch were analyzed by gene expression profiling of a cohort of 22 patient-derived melanoma cell lines. E-cadherin/CDH1 negativity was identified as a surrogate marker for the invasive phenotype. CDH1 expression could be turned on and off by modulating activity of p38 or its downstream target MK2, suggesting that this pathway controls melanoma progression.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-10-14
      DOI: 10.1016/j.jid.2019.08.451
  • Tracing the Equilibrium Phase of Cancer Immunoediting in Epidermal
           Neoplasms via Longitudinal, Intravital Imaging
    • Authors: Bradley J. Kubick; Xiying Fan, Acacia Crouch, Riley McCarthy, Dennis R. Roop
      First page: 891
      Abstract: Recognition of transformed cells by the immune system can sometimes generate a rate-limiting “equilibrium phase,” wherein tumor outgrowth is prevented without complete neoplasm elimination. Targeting premalignancies during this immune-controlled bottleneck is a promising strategy for rational cancer prevention. Thus far, immune equilibrium has been difficult to model in a traceable way and most immunoediting systems have been limited to mesenchymal tumor types. Here, we introduce a mouse model for fluorescent tracing of somatic, epithelial transformation.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-09-19
      DOI: 10.1016/j.jid.2019.08.446
  • Topical Application Of A Mast Cell Stabilizer Improves Impaired Diabetic
           Wound Healing
    • Authors: Ana Tellechea; Sha Bai, Seema Dangwal, Georgios Theocharidis, Masa Nagai, Steffi Koerner, Jae Eun Cheong, Swati Bhasin, Ting-Yu Shih, YongJun Zheng, Wanni Zhao, Cuiping Zhang, Xiaoli Li, Konstantinos Kounas, Smaro Panagiotidou, Theoharis Theoharides, David Mooney, Manoj Bhasin, Lijun Sun, Aristidis Veves
      First page: 901
      Abstract: Impaired wound healing in the diabetic foot is a major problem often leading to amputation. Mast cells have been shown to regulate wound healing in diabetes. We developed an indole-carboxamide type mast cell stabilizer, MCS-01, which proved to be an effective mast cell degranulation inhibitor in vitro and can be delivered topically for prolonged periods through controlled release by specifically designed alginate bandages. In diabetic mice, both pre- and post-wounding, topical MCS-01 application accelerated wound healing comparable to that achieved with systemic mast cell stabilization.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-09-27
      DOI: 10.1016/j.jid.2019.08.449
  • Cells of myeloid origin partly mediate the association between psoriasis
           severity and coronary plaque
    • Authors: Heather L. Teague; Milena Aksentijevich, Elena Stansky, Joanna I. Silverman, Nevin J. Varghese, Amit K. Dey, Youssef Elnabawi, Aditya Goyal, Pradeep K. Dagur, Marcus Y. Chen, J. Philip McCoy, Martin P. Playford, Christopher Hourigan, Joel M. Gelfand, Nehal N. Mehta
      First page: 912
      Abstract: Psoriasis, a chronic inflammatory skin disease is associated with heightened immune activation, accelerated cardiovascular (CV) risk as well as increased acute coronary syndromes, most evident in young adults (Gelfand et al., 2006). This inflammatory skin disease confers an independent risk for myocardial infarction (MI) beyond traditional CV risk factors (Mehta et al., 2010) and on average leads to a decreased lifespan of five years (Gelfand et al., 2006). One explanation is the susceptibility of psoriasis patients to develop unstable, lipid-rich non-calcified coronary plaques (NCB) that are vulnerable to rupture (Lerman et al., 2017).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-09-17
      DOI: 10.1016/j.jid.2019.07.724
  • Staphylococcus aureus Lipoteichoic Acid Initiates a TSLP-Basophil-IL4 Axis
           in the Skin
    • Authors: Anne M. Brauweiler; Elena Goleva, Donald Y.M. Leung
      First page: 915
      Abstract: Atopic Dermatitis (AD) is an inflammatory skin disease associated with increased levels of type 2 cytokines. In addition, the skin of AD patients is frequently colonized with Staphylococcus aureus and increased levels of this pathogen are associated with increased disease severity and elevated type 2 allergic responses (Leung et al., 2019). Recent studies have also shown that the onset of S. aureus colonization correlates with the onset of type 2 responses (Meylan et al., 2017, Nakatsuji et al., 2016), however, a mechanism to explain the induction of type 2 responses by S.
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-09-17
      DOI: 10.1016/j.jid.2019.09.004
  • Inherited Melanoma Risk Variants Associated with Histopathologically
           Amelanotic Melanoma
    • Authors: David Corley Gibbs; Irene Orlow, Steven Vernali, Helen B. Powell, Peter A. Kanetsky, Li Luo, Klaus J. Busam, Ajay Sharma, Anne Kricker, Bruce K. Armstrong, Anne E. Cust, Hoda Anton-Culver, Stephen B. Gruber, Richard P. Gallagher, Roberto Zanetti, Stefano Rosso, Lidia Sacchetto, Terence Dwyer, David W. Ollila, Colin B. Begg, Marianne Berwick, Nancy E. Thomas, GEM Study Group
      First page: 918
      Abstract: Amelanotic melanoma (AM) accounts for 2-20% of cutaneous melanomas but a disproportionately high number of melanoma-related deaths because of a more advanced stage at diagnosis (Strazzulla et al., 2019, Thomas et al., 2014, Wee et al., 2018). AM is defined by lacking pigment upon clinical inspection or melanin upon histopathological examination; and, in some studies, includes both hypo- and non-pigmented lesions. We reported in the Genes, Environment and Melanoma Study (GEM) that carriage of MC1R variants, absent back nevi, many freckles, red hair, lighter eyes, and decreased tannability were associated with histopathologically AM relative to pigmented melanoma (PM) (Vernali et al., 2017), consistent with other studies (Rayner et al., 2019, Strazzulla et al., 2019, Wee et al., 2018).
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-09-27
      DOI: 10.1016/j.jid.2019.09.006
  • Skin microbiota perturbations are distinct and disease severity-dependent
           in hidradenitis suppurativa
    • Authors: Haley B. Naik; Jay-Hyun Jo, Maia Paul, Heidi H. Kong
      First page: 922
      Abstract: Hidradenitis Suppurativa (HS) is a prevalent and debilitating inflammatory skin disease characterized by painful and recurrent nodules and abscesses, malodorous purulent drainage, and disfiguring sinus tract and scar formation involving intertriginous body sites. Microorganisms have been implicated in HS pathogenesis, and broad-spectrum antimicrobial therapy is one of the mainstays of HS management. However, bacteria have been identified in only ∼50% of HS lesions using conventional culture-based methods and no consistent organism has been cultured from HS lesions.(Brook and Frazier, 1999, Gener et al., 2009, Jemec, 2003, Join-Lambert et al., 2011, Leach et al., 1979)
      Citation: Journal of Investigative Dermatology (2019)
      PubDate: 2019-09-17
      DOI: 10.1016/j.jid.2019.08.445
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