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Publisher: Elsevier   (Total: 3163 journals)

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Showing 1 - 200 of 3163 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 9)
AASRI Procedia     Open Access   (Followers: 14)
Academic Pediatrics     Hybrid Journal   (Followers: 30, SJR: 1.655, h-index: 2)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.015, h-index: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 88, SJR: 1.462, h-index: 3)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.932, h-index: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 35, SJR: 1.771, h-index: 3)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 7)
Acta Astronautica     Hybrid Journal   (Followers: 394, SJR: 0.758, h-index: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 1.967, h-index: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.18, h-index: 1)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.128, h-index: 0)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, h-index: 2)
Acta Materialia     Hybrid Journal   (Followers: 244, SJR: 3.263, h-index: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, h-index: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, h-index: 1)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.834, h-index: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.307, h-index: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1, SJR: 1.793, h-index: 6)
Acta Poética     Open Access   (Followers: 4, SJR: 0.101, h-index: 0)
Acta Psychologica     Hybrid Journal   (Followers: 27, SJR: 1.331, h-index: 2)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, h-index: 2)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, h-index: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, h-index: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 6, SJR: 0.19, h-index: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 6)
Acute Pain     Full-text available via subscription   (Followers: 15, SJR: 2.671, h-index: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, h-index: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.29, h-index: 3)
Addictive Behaviors Reports     Open Access   (Followers: 8, SJR: 0.755, h-index: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 2.611, h-index: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Cement Based Materials     Full-text available via subscription   (Followers: 3, SJR: 0.732, h-index: 3)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 135, SJR: 4.09, h-index: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.167, h-index: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.694, h-index: 3)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.277, h-index: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 12, SJR: 2.384, h-index: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 28, SJR: 0.126, h-index: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 10, SJR: 0.992, h-index: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 10, SJR: 1.551, h-index: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 2.089, h-index: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 0.572, h-index: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, h-index: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.686, h-index: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 29, SJR: 3.043, h-index: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 7, SJR: 1.453, h-index: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, h-index: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 3)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, SJR: 0.156, h-index: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.713, h-index: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.316, h-index: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 1.562, h-index: 3)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19, SJR: 1.977, h-index: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, h-index: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 15)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 8)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 23)
Advances in Ecological Research     Full-text available via subscription   (Followers: 42, SJR: 2.524, h-index: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 27, SJR: 1.159, h-index: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 43, SJR: 5.39, h-index: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 53, SJR: 0.591, h-index: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 17)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 1.354, h-index: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 8, SJR: 12.74, h-index: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 1.193, h-index: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.368, h-index: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 11, SJR: 0.749, h-index: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 22)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.193, h-index: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 37, SJR: 4.433, h-index: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.163, h-index: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, h-index: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, h-index: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.682, h-index: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 14, SJR: 0.88, h-index: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 11, SJR: 3.027, h-index: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.694, h-index: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.158, h-index: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, h-index: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 16, SJR: 1.875, h-index: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 6, SJR: 0.174, h-index: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 1.579, h-index: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.461, h-index: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 16, SJR: 1.536, h-index: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.574, h-index: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, h-index: 1)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 8)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 19, SJR: 0.791, h-index: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 59)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, h-index: 1)
Advances in Radiation Oncology     Open Access   (SJR: 0.263, h-index: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, h-index: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 386, SJR: 0.569, h-index: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 10, SJR: 0.555, h-index: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 29, SJR: 2.208, h-index: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 17)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, h-index: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 46, SJR: 1.551, h-index: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, h-index: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 335, SJR: 0.796, h-index: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, h-index: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, h-index: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 10, SJR: 3.671, h-index: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 438, SJR: 1.238, h-index: 3)
Agri Gene     Hybrid Journal   (SJR: 0.13, h-index: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 1.818, h-index: 5)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.156, h-index: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 43, SJR: 1.272, h-index: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 1)
Agriculture and Natural Resources     Open Access   (Followers: 2)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 56, SJR: 1.747, h-index: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, h-index: 3)
Air Medical J.     Hybrid Journal   (Followers: 6, SJR: 0.26, h-index: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, h-index: 0)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 1.153, h-index: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 9)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.604, h-index: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, h-index: 1)
Algal Research     Partially Free   (Followers: 10, SJR: 1.142, h-index: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, h-index: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, h-index: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, h-index: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.201, h-index: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 50, SJR: 4.66, h-index: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4, SJR: 1.796, h-index: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4, SJR: 1.108, h-index: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 50, SJR: 3.267, h-index: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 51, SJR: 1.93, h-index: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 44, SJR: 0.604, h-index: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.524, h-index: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 32, SJR: 7.45, h-index: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.062, h-index: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 34, SJR: 2.973, h-index: 4)
American J. of Medicine     Hybrid Journal   (Followers: 43)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, h-index: 2)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 201, SJR: 2.7, h-index: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 62, SJR: 3.184, h-index: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 6, SJR: 0.265, h-index: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, h-index: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, h-index: 1)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.139, h-index: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 27, SJR: 2.164, h-index: 4)
American J. of Surgery     Hybrid Journal   (Followers: 37, SJR: 1.141, h-index: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, h-index: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, h-index: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 63, SJR: 0.138, h-index: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 15, SJR: 0.411, h-index: 1)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, h-index: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 5, SJR: 4.849, h-index: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 39, SJR: 1.512, h-index: 5)
Analytical Biochemistry     Hybrid Journal   (Followers: 173, SJR: 0.633, h-index: 2)
Analytical Chemistry Research     Open Access   (Followers: 10, SJR: 0.411, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 23, SJR: 0.683, h-index: 2)
Angiología     Full-text available via subscription   (SJR: 0.121, h-index: 0)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1, SJR: 0.111, h-index: 0)

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Journal Cover
Advances in Immunology
Journal Prestige (SJR): 4.433
Citation Impact (citeScore): 6
Number of Followers: 37  
  Full-text available via subscription Subscription journal
ISSN (Print) 0065-2776
Published by Elsevier Homepage  [3163 journals]
  • The Microglial Response to Neurodegenerative Disease
    • Authors: Wilbur M. Song; Marco Colonna
      Abstract: Publication date: Available online 9 May 2018
      Source:Advances in Immunology
      Author(s): Wilbur M. Song, Marco Colonna
      Microglia are a subset of tissue macrophages that constitute the major immune cell type of the central nervous system. These cells have long been known to change their morphology and functions in response to various neurological insults. Recently, a plethora of unbiased transcriptomics studies have revealed that across a broad spectrum of neurodegeneration-like disease models, microglia adopt a similar activation signature and perform similar functions. Despite these commonalities in response, the role of microglia has been described as both positive and negative in different murine disease models. In humans, genetic association studies have revealed strong connections between microglia genes and various neurodegenerative diseases, and mechanistic investigations of these mutations have added another layer of complexity. Here, we provide an overview of studies that have built a case for a common microglial response to neurodegeneration and discuss pathways that may be important to initiate and sustain this response; delineate the multifaceted functions of activated microglia spanning different diseases; and discuss insights from studying genes associated with disease in humans. We argue that strong evidence causally links activated microglia function to neurodegeneration and discuss what seems to be a conflict between mouse models and human genetics.

      PubDate: 2018-05-28T11:31:15Z
      DOI: 10.1016/
  • The First B-Cell Tolerance Checkpoint in Mice and Humans: Control by AID
    • Authors: Masayuki Kuraoka; Eric Meffre; Garnett Kelsoe
      Abstract: Publication date: Available online 7 May 2018
      Source:Advances in Immunology
      Author(s): Masayuki Kuraoka, Eric Meffre, Garnett Kelsoe
      Activation-induced cytidine deaminase (AID) expression in the germinal center response drives the immunoglobulin class-switch recombination and V(D)J hypermutation necessary for efficacious, high-affinity antibody responses. That AID is expressed in developing lymphocytes is less well known, but represents an evolutionarily conserved pattern of lymphocyte development that is represented in all vertebrate species. Here we review the role of early, developmentally regulated AID expression in mice and humans and its role in establishing the first B-cell tolerance checkpoint. This newly recognized component of central tolerance requires coordinate signaling by poly- or autoreactive B-cell antigen receptors and endosomal Toll-like receptors. These signals synergize to upregulate AID expression in immature and transitional B cells to levels that approach that of germinal center B cells with the result of caspase 3-mediated cell death. In this review, we discuss the origins and mechanism of this interesting collaboration between adaptive and innate receptors to purge the primary B-cell repertoire of self-reactivity and how it may be related to receptor editing, the other major mechanism for central tolerance.

      PubDate: 2018-05-28T11:31:15Z
      DOI: 10.1016/
  • Series Page
    • Abstract: Publication date: 2018
      Source:Advances in Immunology, Volume 138

      PubDate: 2018-05-28T11:31:15Z
  • Molecular Aspects of Allergens and Allergy
    • Authors: Rudolf Valenta; Alexander Karaulov; Verena Niederberger; Pia Gattinger; Marianne van Hage; Sabine Flicker; Birgit Linhart; Raffaela Campana; Margarete Focke-Tejkl; Mirela Curin; Julia Eckl-Dorna; Christian Lupinek; Yvonne Resch-Marat; Susanne Vrtala; Irene Mittermann; Victoria Garib; Musa Khaitov; Peter Valent; Winfried F. Pickl
      Abstract: Publication date: Available online 26 April 2018
      Source:Advances in Immunology
      Author(s): Rudolf Valenta, Alexander Karaulov, Verena Niederberger, Pia Gattinger, Marianne van Hage, Sabine Flicker, Birgit Linhart, Raffaela Campana, Margarete Focke-Tejkl, Mirela Curin, Julia Eckl-Dorna, Christian Lupinek, Yvonne Resch-Marat, Susanne Vrtala, Irene Mittermann, Victoria Garib, Musa Khaitov, Peter Valent, Winfried F. Pickl
      Immunoglobulin E (IgE)-associated allergy is the most common immune disorder. More than 30% of the population suffer from symptoms of allergy which are often severe, disabling, and life threatening such as asthma and anaphylaxis. Population-based birth cohort studies show that up to 60% of the world population exhibit IgE sensitization to allergens, of which most are protein antigens. Thirty years ago the first allergen-encoding cDNAs have been isolated. In the meantime, the structures of most of the allergens relevant for disease in humans have been solved. Here we provide an update regarding what has been learned through the use of defined allergen molecules (i.e., molecular allergology) and about mechanisms of allergic disease in humans. We focus on new insights gained regarding the process of sensitization to allergens, allergen-specific secondary immune responses, and mechanisms underlying allergic inflammation and discuss open questions. We then show how molecular forms of diagnosis and specific immunotherapy are currently revolutionizing diagnosis and treatment of allergic patients and how allergen-specific approaches may be used for the preventive eradication of allergy.

      PubDate: 2018-05-02T08:43:54Z
      DOI: 10.1016/
  • Eosinophil Development, Disease Involvement, and Therapeutic Suppression
    • Authors: Patricia C. Fulkerson; Marc E. Rothenberg
      Abstract: Publication date: Available online 22 April 2018
      Source:Advances in Immunology
      Author(s): Patricia C. Fulkerson, Marc E. Rothenberg
      Human eosinophils have characteristic morphologic features, including a bilobed nucleus and cytoplasmic granules filled with cytotoxic and immunoregulatory proteins that are packaged in a specific manner. Eosinophil production in the bone marrow is exquisitely regulated by timely expression of a repertoire of transcription factors that work together via collaborative and hierarchical interactions to direct eosinophil development. In addition, proper granule formation, which occurs in a spatially organized manner, is an intrinsic checkpoint that must be passed for proper eosinophil production to occur. In eosinophil-associated disorders, eosinophils and their progenitors can be recruited in large numbers into tissues where they can induce proinflammatory organ damage in response to local signals. Eosinophils are terminally differentiated and do not proliferate once they leave the bone marrow. The cytokine IL-5 specifically enhances eosinophil production and, along with other mediators, promotes eosinophil activation. Indeed, eosinophil depletion with anti-IL-5 or anti-IL-5Rα is now proven to be clinically beneficial for several eosinophilic disorders, most notably severe asthma, and several therapeutics targeting eosinophil viability and production are now in development. Significant progress has been made in our understanding of eosinophil development and the consequences of tissue eosinophilia. Future research efforts focused on basic eosinophil immunobiology and translational efforts to assist in the diagnosis, treatment selection, and resolution of eosinophil-associated disorders will likely be informative and clinically helpful.

      PubDate: 2018-04-25T08:00:59Z
      DOI: 10.1016/
  • Molecular Classification of Primary Immunodeficiencies of T Lymphocytes
    • Authors: William A. Comrie; Michael J. Lenardo
      Abstract: Publication date: Available online 29 March 2018
      Source:Advances in Immunology
      Author(s): William A. Comrie, Michael J. Lenardo
      Proper regulation of the immune system is required for protection against pathogens and preventing autoimmune disorders. Inborn errors of the immune system due to inherited or de novo germline mutations can lead to the loss of protective immunity, aberrant immune homeostasis, and the development of autoimmune disease, or combinations of these. Forward genetic screens involving clinical material from patients with primary immunodeficiencies (PIDs) can vary in severity from life-threatening disease affecting multiple cell types and organs to relatively mild disease with susceptibility to a limited range of pathogens or mild autoimmune conditions. As central mediators of innate and adaptive immune responses, T cells are critical orchestrators and effectors of the immune response. As such, several PIDs result from loss of or altered T cell function. PID-associated functional defects range from complete absence of T cell development to uncontrolled effector cell activation. Furthermore, the gene products of known PID causal genes are involved in diverse molecular pathways ranging from T cell receptor signaling to regulators of protein glycosylation. Identification of the molecular and biochemical cause of PIDs can not only guide the course of treatment for patients, but also inform our understanding of the basic biology behind T cell function. In this chapter, we review PIDs with known genetic causes that intrinsically affect T cell function with particular focus on perturbations of biochemical pathways.

      PubDate: 2018-04-15T08:43:10Z
      DOI: 10.1016/
  • Chemokines: Critical Regulators of Memory T Cell Development, Maintenance,
           and Function
    • Authors: Rod A. Rahimi; Andrew D. Luster
      Abstract: Publication date: Available online 26 March 2018
      Source:Advances in Immunology
      Author(s): Rod A. Rahimi, Andrew D. Luster
      Memory T cells are central to orchestrating antigen-specific recall responses in vivo. Compared to naïve T cells, memory T cells respond more quickly to cognate peptide:MHC with a shorter lag time for entering the cell cycle and exerting effector functions. However, it is now well established that this enhanced responsiveness is not the only mechanism whereby memory T cells are better equipped than naïve T cells to rapidly and robustly induce inflammation. In contrast to naïve T cells, memory T cells are composed of distinct subsets with unique trafficking patterns and localizations. Tissue-resident memory T cells persist in previously inflamed tissue and function as first responders to cognate antigen reexposure. In addition, a heterogeneous group of circulating memory T cells augment inflammation by either rapidly migrating to inflamed tissue or responding to cognate antigen within secondary lymphoid organs and producing additional effector T cells. Defining the mechanisms regulating T cell positioning and trafficking and how this influences the development, maintenance, and function of memory T cell subsets is essential to improving vaccine design as well as treatment of immune-mediated diseases. In this chapter, we will review our current knowledge of how chemokines, critical regulators of cell positioning and migration, govern memory T cell biology in vivo. In addition, we discuss areas of uncertainty and future directions for further delineating how T cell localization influences memory T cell biology.

      PubDate: 2018-04-15T08:43:10Z
      DOI: 10.1016/
  • Unexpected Roles for Intracellular Complement in the Regulation of Th1
    • Authors: Erin E. West; Behdad Afzali; Claudia Kemper
      Abstract: Publication date: Available online 26 March 2018
      Source:Advances in Immunology
      Author(s): Erin E. West, Behdad Afzali, Claudia Kemper
      The complement system is generally recognized as an evolutionarily ancient and critical part of innate immunity required for the removal of pathogens that have breached the protective host barriers. It was originally defined as a liver-derived serum surveillance system that induces the opsonization and killing of invading microbes and amplifies the general inflammatory reactions. However, studies spanning the last four decades have established complement also as a vital bridge between innate and adaptive immunity. Furthermore, recent work on complement, and in particular its impact on human T helper 1 (Th1) responses, has led to the unexpected findings that the complement system also functions within cells and that it participates in the regulation of basic processes of the cell, including metabolism. These recent new insights into the unanticipated noncanonical activities of this ancient system suggest that the functions of complement extend well beyond mere host protection and into cellular physiology.

      PubDate: 2018-04-15T08:43:10Z
      DOI: 10.1016/
  • Series Page
    • Abstract: Publication date: 2018
      Source:Advances in Immunology, Volume 137

      PubDate: 2018-02-24T23:27:35Z
  • The Fate Choice Between Effector and Memory T Cell Lineages: Asymmetry,
           Signal Integration, and Feedback to Create Bistability
    • Authors: Ronald A. Backer; Pleun Hombrink; Christina Helbig; Derk Amsen
      Abstract: Publication date: Available online 1 February 2018
      Source:Advances in Immunology
      Author(s): Ronald A. Backer, Pleun Hombrink, Christina Helbig, Derk Amsen
      CD8+ T cells clear primary infections with intracellular pathogens and provide long-term immunity against reinfection. Two different types of CD8+ T cells are responsible for these functions: short-lived effector T cells and memory T cells. The cellular relationship between these two types of CD8+ T cells has been subject to much investigation. Both cell types can derive from a single naïve CD8+ T cell precursor. Their generation requires a fate choice early during a T cell response. As a result, two populations of T cells emerge. One of these consists of terminally differentiated short-lived effector T cells. The other contains cells able to develop into long-lived memory T cells. A foundation for development of these two populations may be laid during the first division of an activated naïve T cell precursor, as a consequence of asymmetric segregation of fate-determining factors into the daughter cells. Nonetheless, the binary choice between the two lineages is strongly influenced by signals, which ensure that the differentiation process is matched with the needs posed by the infection. Here, we will discuss the genetic and metabolic programs governing differentiation of these two lineages as well as the processes leading to their induction and consolidation to create bistability. These processes involve extensive lateral inhibition between the programs as well as positive feedback between the genetic programs and the signaling pathways responsible for their induction. These features will be highlighted by discussing the role of the Notch signaling pathway in guiding the decision between the two lineages.

      PubDate: 2018-02-02T19:37:34Z
      DOI: 10.1016/
  • Single-Cell Resolution of T Cell Immune Responses
    • Authors: Veit R. Buchholz; Michael Flossdorf
      Abstract: Publication date: Available online 9 January 2018
      Source:Advances in Immunology
      Author(s): Veit R. Buchholz, Michael Flossdorf
      Single antigen-specific B or T lymphocytes are the smallest functional units, into which an adaptive immune response can be dissected. Today, novel high-throughput technologies are providing researches with increasingly complex information on the diverse phenotypic signatures of individual lymphocytes. With a focus on T cells, we summarize here, how computational approaches are becoming increasingly important to identify the relevant developmental boundaries and connections between these high-dimensional lymphocyte states. We then describe how these insights may be further expanded by novel experimental approaches that allow to map the fate of individual T cells and their progeny in vivo and in vitro. Finally, we highlight how these experiments have uncovered a probabilistic regulatory structure of T cell immune responses and briefly discuss, how two distinct theoretical frameworks used to describe this structure may be merged to best capture single T cell behavior in computational terms.

      PubDate: 2018-01-09T20:25:31Z
      DOI: 10.1016/
  • Caveolin-1: The Unnoticed Player in TCR and BCR Signaling
    • Authors: Gina J. Fiala; Susana Minguet
      Pages: 83 - 133
      Abstract: Publication date: Available online 13 February 2018
      Source:Advances in Immunology
      Author(s): Gina J. Fiala, Susana Minguet
      T and B lymphocytes are key players of the adaptive immune system. They recognize pathogenic cues via the T cell antigen receptor (TCR) and the B cell antigen receptor (BCR) to get activated and execute their protective function. TCR and BCR signaling are initiated at the plasma membrane and subsequently propagated into the cell, ultimately leading to cell activation and a protective immune response. However, inappropriate activation of T and B cells can be detrimental to the host resulting in autoimmune disorders, immunodeficiencies, and cancer. The TCR and BCR are located at the plasma membrane, which composition is highly heterogenic. Membrane compartmentalization based on specific lipid–lipid and protein–lipid interactions has raised the interest of the scientific community, converting the plasma membrane into an active player in the initiation of signaling and adding an additional layer of regulation to our current understanding of the functioning of antigen receptors. Caveolin-1 is an integral membrane protein and a crucial component of caveolae. It has been long thought that lymphocytes lack Caveolin-1 expression, due to the absence of detectable caveolae in lymphocytes and the failure to detect Caveolin-1 in T and B cell lines. However, Caveolin-1 is expressed at low levels in primary lymphocytes, and recent studies have shown the importance of Caveolin-1 for the basal membrane organization of the BCR and the TCR as well as their reorganization upon activation. Here, we review our current understanding of the initial signaling events of TCR and BCR activation with respect to receptor compartmentalization on the plasma membrane and with special emphasis on the previously unnoticed role of Caveolin-1.

      PubDate: 2018-02-14T19:27:37Z
      DOI: 10.1016/
  • The Unusual Genetics and Biochemistry of Bovine Immunoglobulins
    • Authors: Robyn L. Stanfield; Jeremy Haakenson; Thaddeus C. Deiss; Michael F. Criscitiello; Ian A. Wilson; Vaughn V. Smider
      Pages: 135 - 164
      Abstract: Publication date: Available online 9 February 2018
      Source:Advances in Immunology
      Author(s): Robyn L. Stanfield, Jeremy Haakenson, Thaddeus C. Deiss, Michael F. Criscitiello, Ian A. Wilson, Vaughn V. Smider
      Antibodies are the key circulating molecules that have evolved to fight infection by the adaptive immune system of vertebrates. Typical antibodies of most species contain six complementarity-determining regions (CDRs), where the third CDR of the heavy chain (CDR H3) has the greatest diversity and often makes the most significant contact with antigen. Generally, the process of V(D)J recombination produces a vast repertoire of antibodies; multiple V, D, and J gene segments recombine with additional junctional diversity at the V-D and D-J joints, and additional combinatorial possibilities occur through heavy- and light-chain pairing. Despite these processes, the overall structure of the resulting antibody is largely conserved, and binding to antigen occurs predominantly through the CDR loops of the immunoglobulin V domains. Bovines have deviated from this general paradigm by having few VH regions and thus little germline combinatorial diversity, but their antibodies contain long CDR H3 regions, with substantial diversity generated through somatic hypermutation. A subset of the repertoire comprises antibodies with ultralong CDR H3s, which can reach over 70 amino acids in length. Structurally, these unusual antibodies form a β-ribbon “stalk” and disulfide-bonded “knob” that protrude far from the antibody surface. These long CDR H3s allow cows to mount a particularly robust immune response when immunized with viral antigens, particularly to broadly neutralizing epitopes on a stabilized HIV gp140 trimer, which has been a challenge for other species. The unusual genetics and structural biology of cows provide for a unique paradigm for creation of immune diversity and could enable generation of antibodies against especially challenging targets and epitopes.

      PubDate: 2018-02-14T19:27:37Z
      DOI: 10.1016/
  • Series Page
    • Abstract: Publication date: 2017
      Source:Advances in Immunology, Volume 136

      PubDate: 2017-09-28T03:36:02Z
  • G Protein-Coupled Kinin Receptors and Immunity Against Pathogens
    • Authors: Julio Scharfstein; Pablo I.P. Ramos; Manoel Barral-Netto
      Abstract: Publication date: Available online 23 August 2017
      Source:Advances in Immunology
      Author(s): Julio Scharfstein, Pablo I.P. Ramos, Manoel Barral-Netto
      For decades, immunologists have considered the complement system as a paradigm of a proteolytic cascade that, acting cooperatively with the immune system, enhances host defense against infectious organisms. In recent years, advances made in thrombosis research disclosed a functional link between activated neutrophils, monocytes, and platelet-driven thrombogenesis. Forging a physical barrier, the fibrin scaffolds generated by synergism between the extrinsic and intrinsic (contact) pathways of coagulation entrap microbes within microvessels, limiting the systemic spread of infection while enhancing the clearance of pathogens by activated leukocytes. Insight from mice models of thrombosis linked fibrin formation via the intrinsic pathway to the autoactivation of factor XII (FXII) by negatively charged "contact" substances, such as platelet-derived polyphosphates and DNA from neutrophil extracellular traps. Following cleavage by FXIIa, activated plasma kallikrein (PK) initiates inflammation by liberating the nonapeptide bradykinin (BK) from an internal domain of high molecular weight kininogen (HK). Acting as a paracrine mediator, BK induces vasodilation and increases microvascular permeability via activation of endothelial B2R, a constitutively expressed subtype of kinin receptor. During infection, neutrophil-driven extravasation of plasma fuels inflammation via extravascular activation of the kallikrein-kinin system (KKS). Whether liberated by plasma-borne PK, tissue kallikrein, and/or microbial-derived proteases, the short-lived kinins activate immature dendritic cells via B2R, thus linking the infection-associated innate immunity/inflammation to the adaptive arm of immunity. As inflammation persists, a GPI-linked carboxypeptidase M removes the C-terminal arginine from the primary kinin, converting the B2R agonist into a high-affinity ligand for B1R, a GPCR subtype that is transcriptionally upregulated in injured/inflamed tissues. As reviewed here, lessons taken from studies of kinin receptor function in experimental infections have shed light on the complex proteolytic circuits that, acting at the endothelial interface, reciprocally couple immunity to the proinflammatory KKS.

      PubDate: 2017-08-27T22:10:24Z
      DOI: 10.1016/
  • Series Page
    • Abstract: Publication date: 2017
      Source:Advances in Immunology, Volume 135

      PubDate: 2017-08-27T22:10:24Z
  • Complement System in Neural Synapse Elimination in Development and Disease
    • Authors: Jessy Presumey; Allison R. Bialas; Michael C. Carroll
      Abstract: Publication date: Available online 31 July 2017
      Source:Advances in Immunology
      Author(s): Jessy Presumey, Allison R. Bialas, Michael C. Carroll
      Recent discoveries implicate the classical complement cascade in normal brain development and in disease. Complement proteins C1q, C3, and C4 participate in synapse elimination, tagging inappropriate synaptic connections between neurons for removal by phagocytic microglia that exist in a special, highly phagocytic state during the synaptic pruning period. Several neurodevelopmental disorders, such as schizophrenia and autism, are thought to be caused by an imbalance in synaptic pruning, and recent studies suggest that dysregulation of complement could promote this synaptic pruning imbalance. Moreover, in the mature brain, complement can be aberrantly activated in early stages of neurodegenerative diseases to stimulate synapse loss. Similar pathways can also be activated in response to inflammation, as in West Nile Virus infection or in lupus, where peripheral inflammation can promote microglia-mediated synapse loss. Whether synapse loss in disease is a true reactivation of developmental synaptic pruning programs remains unclear; nonetheless, complement proteins represent potential therapeutic targets for both neurodevelopmental and neurodegenerative diseases.

      PubDate: 2017-08-08T05:36:16Z
      DOI: 10.1016/
  • β2-Adrenoceptor Function in Asthma
    • Authors: Yassine Amrani; Peter Bradding
      Abstract: Publication date: Available online 27 July 2017
      Source:Advances in Immunology
      Author(s): Yassine Amrani, Peter Bradding
      β2-adrenoceptor agonists, often used in combination with corticosteroids, have been extensively used for the treatment of asthma. However, concerns have been raised regarding their adverse effects and safety including poor asthma control, life-threatening exacerbations, exacerbations that often require hospitalization, and asthma-related deaths. The question as to whether these adverse effects relate to the loss of their bronchoprotective action remains an interesting possibility. In the chapter, we will review the experimental evidence that describes the different potential factors and associated mechanisms that can blunt the therapeutic action of β2-adrenoceptor agonists in asthma. We show here evidence that various key inflammatory cytokines, growth factors, some respiratory viruses, certain allergens, unknown factors present in serum from atopic asthmatics have the capacity to impair β2-adrenoceptor function in airway smooth muscle, the main target of these drugs. More importantly, we present our latest research describing the role played by mast cells in impairing β2-adrenoceptor function. Although no definitive conclusion could be made regarding the implication of one single mechanism, receptor uncoupling, or receptor desensitization due to phosphorylation represents the main inhibitory pathways associated with a loss of β2-adrenoceptor function in airway smooth muscle. Targeting the pathways leading to β2-adrenoceptor dysfunction will likely provide novel therapies to improve the efficacy of β2-agonists in asthma.

      PubDate: 2017-07-30T07:22:52Z
      DOI: 10.1016/
  • Emerging Roles for MAS-Related G Protein-Coupled Receptor-X2 in Host
    • Authors: Hydar Ali
      Abstract: Publication date: Available online 24 July 2017
      Source:Advances in Immunology
      Author(s): Hydar Ali
      Mast cells (MCs) are tissue-resident immune cells that contribute to host defense but are best known for their roles in allergic and inflammatory diseases. In humans, MCs are divided into two subtypes based on the protease content of their secretory granules. Thus, human lung MCs contain only tryptase and are known as MCT, whereas skin MCs contain both tryptase and chymase and are known as MCTC. Patients with severe asthma display elevated MCs in the lung, which undergo phenotypic change from MCT to MCTC. Although the human genome contains four Mas related G protein coupled receptor X (MRGPRX) genes, an important feature of MCTC is that they selectively express MRGPRX2. It is activated by antimicrobial host defense peptides such as human β-defensins and the cathelicidin LL-37 and likely contributes to host defense. MRGPRX2 is also a receptor for the neuropeptide substance P, major basic protein, eosinophil peroxidase, opioids, and many FDA-approved cationic drugs. Increased expression of MRGPRX2 or enhanced downstream signaling likely contributes to chronic inflammatory diseases such as rosacea, atopic dermatitis, chronic urticaria, and severe asthma. In this chapter, I will discuss the expression profile and function of MRGPRX1-4 and review the emerging roles of MRGPRX2 on host defense, chronic inflammatory diseases, and drug-induced pseudoallergic reactions. I will also examine the novel aspects of MRGPRX2 signaling in MCs as it related to degranulation and review the mechanisms of its regulation.

      PubDate: 2017-07-30T07:22:52Z
      DOI: 10.1016/
  • Chromosome 17q21 Genes ORMDL3 and GSDMB in Asthma and Immune Diseases
    • Authors: Sudipta Das; Marina Miller; David H. Broide
      Abstract: Publication date: Available online 19 July 2017
      Source:Advances in Immunology
      Author(s): Sudipta Das, Marina Miller, David H. Broide
      Chromosome 17q21 contains a cluster of genes including ORMDL3 and GSDMB, which have been highly linked to asthma in genome-wide association studies. ORMDL3 is localized to the endoplasmic reticulum and regulates downstream pathways including sphingolipids, metalloproteases, remodeling genes, and chemokines. ORMDL3 inhibits serine palmitoyl-CoA transferase, the rate-limiting enzyme for sphingolipid biosynthesis. In addition, ORMDL3 activates the ATF6α branch of the unfolded protein response which regulates SERCA2b and IL-6, pathways of potential importance to asthma. The SNP-linking chromosome 17q21 to asthma is associated with increased ORMDL3 and GSDMB expression. Mice expressing either increased levels of human ORMDL3, or human GSDMB, have an asthma phenotype characterized by increased airway responsiveness and increased airway remodeling (increased smooth muscle and fibrosis) in the absence of airway inflammation. GSDMB regulates expression of 5-LO and TGF-β1 which are known pathways involved in the pathogenesis of asthma. GSDMB is one of four members of the GSDM family (GSDMA, GSDMB, GSDMC, and GSDMD). GSDMD (located on chromosome 8q24 and not linked to asthma) has emerged as a key mediator of pyroptosis. GSDMD is a key component of the NLPR3 inflammasome and is required for its activation. GSDMD undergoes proteolytic cleavage by caspase-1 to release its N-terminal fragment, which in turn mediates pyroptosis and IL-1β secretion. Chromosome 17q21 has not only been linked to asthma but also to type 1 diabetes, inflammatory bowel disease, and primary biliary cirrhosis suggesting that future insights into the biology of genes located in this region will increase our understanding of these diseases.

      PubDate: 2017-07-24T02:44:09Z
      DOI: 10.1016/
  • Roles of NHERF Family of PDZ-Binding Proteins in Regulating GPCR Functions
    • Authors: David Broadbent; Mohammad M. Ahmadzai; Ananth K. Kammala; Canchai Yang; Christopher Occhiuto; Rupali Das; Hariharan Subramanian
      Abstract: Publication date: Available online 11 July 2017
      Source:Advances in Immunology
      Author(s): David Broadbent, Mohammad M. Ahmadzai, Ananth K. Kammala, Canchai Yang, Christopher Occhiuto, Rupali Das, Hariharan Subramanian
      Multicellular organisms are equipped with an array of G-protein-coupled receptors (GPCRs) that mediate cell–cell signaling allowing them to adapt to environmental cues and ultimately survive. This is mechanistically possible through complex intracellular GPCR machinery that encompasses a vast network of proteins. Within this network, there is a group called scaffolding proteins that facilitate proper localization of signaling proteins for a quick and robust GPCR response. One protein family within this scaffolding group is the PSD-95/Dlg/ZO-1 (PDZ) family which is important for GPCR localization, internalization, recycling, and downstream signaling. Although the PDZ family of proteins regulate the functions of several receptors, this chapter focuses on a subfamily within the PDZ protein family called the Na+/H+ exchanger regulatory factors (NHERFs). Here we extensively review the predominantly characterized roles of NHERFs in renal phosphate absorption, intestinal ion regulation, cancer progression, and immune cell functions. Finally, we discuss the future perspectives and possible clinical application of targeting NHERFs in several disorders.

      PubDate: 2017-07-13T02:08:53Z
      DOI: 10.1016/
  • GPCR Signaling in C. elegans and Its Implications in Immune Response
    • Authors: Anjali Gupta; Varsha Singh
      Abstract: Publication date: Available online 23 June 2017
      Source:Advances in Immunology
      Author(s): Anjali Gupta, Varsha Singh
      The ability to sense environmental cues is central to the survival of living organisms. G-protein-coupled receptors (GPCRs) are, by far, the most diverse class of sensory receptors and play an important role in surveillance. As Caenorhabditis elegans lives in soil and feeds on bacteria, it must have strategies to differentiate between nutritious vs pathogenic bacteria. In C. elegans, lacking professional immune cells, GPCRs play a very important role in defense responses, for survival against pathogens. Here, we review a rich body of research to show that C. elegans uses GPCRs in different tissues for immune surveillance, immune homeostasis, as well as behavioral responses. Nematode sensory neurons and GPCRs can sense both pathogen-associated molecules as well as damage-associated molecular patterns during infection. Both fight and flight responses, activated upon exposure to pathogens, are driven by GPCRs and trimeric G proteins in the sensory neurons.

      PubDate: 2017-06-24T01:01:49Z
      DOI: 10.1016/
  • Canonical and Noncanonical Signaling Roles of β-Arrestins in
           Inflammation and Immunity
    • Authors: Mohammad M. Ahmadzai; David Broadbent; Christopher Occhiuto; Canchai Yang; Rupali Das; Hariharan Subramanian
      Abstract: Publication date: Available online 16 June 2017
      Source:Advances in Immunology
      Author(s): Mohammad M. Ahmadzai, David Broadbent, Christopher Occhiuto, Canchai Yang, Rupali Das, Hariharan Subramanian
      β-Arrestins are a highly conserved family of cytosolic adaptor proteins that contribute to many immune functions by orchestrating the desensitization and internalization of cell-surface G protein-coupled receptors (GPCRs) via well-studied canonical interactions. In cells of the innate and adaptive immune system, β-arrestins also subserve a parallel but less understood role in which they propagate, rather than terminate, intracellular signal transduction cascades. Because β-arrestins are promiscuous in their binding, they are capable of interacting with several different GPCRs and downstream effectors; in doing so, they vastly expand the repertoire of cellular responses evoked by agonist binding and the scope of responses that may contribute to inflammation during infectious and sterile insults. In this chapter, we attempt to provide an overview of the canonical and noncanonical roles of β-arrestins in inflammatory diseases.

      PubDate: 2017-06-24T01:01:49Z
      DOI: 10.1016/
  • Adhesion GPCRs in Regulating Immune Responses and Inflammation
    • Authors: Hsi-Hsien Lin; Cheng-Chih Hsiao; Caroline Pabst; Josée Hébert; Torsten Schöneberg; Jörg Hamann
      Abstract: Publication date: Available online 13 June 2017
      Source:Advances in Immunology
      Author(s): Hsi-Hsien Lin, Cheng-Chih Hsiao, Caroline Pabst, Josée Hébert, Torsten Schöneberg, Jörg Hamann
      The adhesion family comprises one of the five major clades of G protein-coupled receptors (GPCRs). Unlike conventional GPCRs, adhesion GPCRs (aGPCRs) have extended ectodomains with various protein folds that facilitate protein–protein interactions and, hence, putative cellular adhesive functions. Juxtaposed to the seven-pass transmembrane domain is a GPCR autoproteolysis-inducing domain that enables autoproteolytic cleavage of the receptor, resulting in a bipartite structure of many aGPCRs. aGPCRs are widely distributed and play critical roles in many developmental processes; yet, the underlying mechanisms of activation and signal transduction have emerged only recently. About one-third of the 33 human aGPCRs are expressed in hematopoietic stem, progenitor, or mature cells, where they define distinct cellular populations. Recent studies have demonstrated roles of aGPCR in the control of innate effector functions and the susceptibility for and onset of (auto)inflammatory conditions. We here discuss the current knowledge about aGPCRs in the regulation of immune responses and inflammation.

      PubDate: 2017-06-14T00:27:24Z
      DOI: 10.1016/
  • P2Y Receptors in Immune Response and Inflammation
    • Authors: Diana Le Duc; Angela Schulz; Vera Lede; Annelie Schulze; Doreen Thor; Antje Brüser; Torsten Schöneberg
      Abstract: Publication date: Available online 10 June 2017
      Source:Advances in Immunology
      Author(s): Diana Le Duc, Angela Schulz, Vera Lede, Annelie Schulze, Doreen Thor, Antje Brüser, Torsten Schöneberg
      Metabotropic pyrimidine and purine nucleotide receptors (P2Y receptors) are expressed in virtually all cells with implications in very diverse biological functions, including the well-established platelet aggregation (P2Y12), but also immune regulation and inflammation. The classical P2Y receptors bind nucleotides and are encoded by eight genes with limited sequence homology, while phylogenetically related receptors (e.g., P2Y12-like) recognize lipids and peptides, but also nucleotide derivatives. Growing lines of evidence suggest an important function of P2Y receptors in immune cell differentiation and maturation, migration, and cell apoptosis. Here, we give a perspective on the P2Y receptors' molecular structure and physiological importance in immune cells, as well as the related diseases and P2Y-targeting therapies. Extensive research is being undertaken to find modulators of P2Y receptors and uncover their physiological roles. We anticipate the medical applications of P2Y modulators and their immune relevance.

      PubDate: 2017-06-14T00:27:24Z
      DOI: 10.1016/
  • G Protein-Coupled Receptor Kinases in the Inflammatory Response and
    • Authors: Michael D. Steury; Laura R. McCabe; Narayanan Parameswaran
      Abstract: Publication date: Available online 10 June 2017
      Source:Advances in Immunology
      Author(s): Michael D. Steury, Laura R. McCabe, Narayanan Parameswaran
      G protein-coupled receptor kinases (GRKs) are serine/threonine kinases that regulate a large and diverse class of G protein-coupled receptors (GPCRs). Through GRK phosphorylation and β-arrestin recruitment, GPCRs are desensitized and their signal terminated. Recent work on these kinases has expanded their role from canonical GPCR regulation to include noncanonical regulation of non-GPCR and nonreceptor substrates through phosphorylation as well as via scaffolding functions. Owing to these and other regulatory roles, GRKs have been shown to play a critical role in the outcome of a variety of physiological and pathophysiological processes including chemotaxis, signaling, migration, inflammatory gene expression, etc. This diverse set of functions for these proteins makes them popular targets for therapeutics. Role for these kinases in inflammation and inflammatory disease is an evolving area of research currently pursued in many laboratories. In this review, we describe the current state of knowledge on various GRKs pertaining to their role in inflammation and inflammatory diseases.

      PubDate: 2017-06-14T00:27:24Z
      DOI: 10.1016/
  • Emerging Roles of Regulators of G Protein Signaling (RGS) Proteins in the
           Immune System
    • Authors: Kirk Druey
      Abstract: Publication date: Available online 29 May 2017
      Source:Advances in Immunology
      Author(s): Kirk M. Druey
      The regulators of G protein signaling (RGS) proteins are a large, evolutionarily conserved group of intracellular proteins expressed in every cell type and tissue throughout the body including the immune system. Through their signature GTPase-activating protein (GAP) activity on heterotrimeric G proteins and interactions with signaling complexes and membrane constituents (e.g., lipids), RGS proteins determine the intensity and duration of G protein-coupled receptor-induced responses. They may also have a function in generating intracellular signaling gradients necessary for the directional migration of leukocytes to inflamed tissues containing local accumulations of chemoattractants. Although physiological functions of most RGS proteins in leukocytes and lymphoid organs are largely unknown, it appears thus far that deficiency of individual RGS proteins in mice does not affect homeostatic immune responses in the absence of immunogenic challenge and/or microbial infection. Although aberrant expression of some RGS proteins has been linked to dysregulated immunity and/or neoplasia in humans, there are no human diseases attributed to specific RGS dysfunction. Here, we highlight mostly published work describing expression and functions of the core group of RGS proteins that were among the first discovered, in both innate and adaptive immune processes, with particular emphasis on cell trafficking.

      PubDate: 2017-05-29T23:24:28Z
  • Chemokine-Driven CD4+ T Cell Homing: New Concepts and Recent Advances
    • Authors: Carly E. Gregor; Jade Foeng; Iain Comerford; Shaun R. McColl
      Abstract: Publication date: Available online 28 April 2017
      Source:Advances in Immunology
      Author(s): Carly E. Gregor, Jade Foeng, Iain Comerford, Shaun R. McColl
      CD4+ T cells are critical regulators of the adaptive immune system and have diverse roles in regulating responses to the broad array of microbes encountered. Appropriate execution of their effector function requires precise and coordinated migration of these cells to specific lymphoid niches and peripheral sites. This migration is largely controlled by dynamic expression of chemokine receptors and the discrete functions of distinct subsets of CD4+ T cells can often be determined from their expression of specific chemokine receptors. In this chapter, we discuss recent advances in the subset-specific homing of distinct T helper populations, focusing on new insights stemming from the increased diversity and plasticity now observed among CD4+ T cells as well as how chemokine receptors can govern T cell-fate decisions. We also discuss current understanding of CD4+ memory T cells with reference to their diversification based on chemokine receptor expression.

      PubDate: 2017-05-04T10:24:06Z
      DOI: 10.1016/
  • Series Page
    • Abstract: Publication date: 2017
      Source:Advances in Immunology, Volume 134

      PubDate: 2017-04-14T04:09:22Z
  • Chapter Five Humanized Immunoglobulin Mice
    • Authors: Laurent Verkoczy
      Abstract: Publication date: 2017
      Source:Advances in Immunology, Volume 134
      Author(s): Laurent Verkoczy
      A vaccine that can effectively prevent HIV-1 transmission remains paramount to ending the HIV pandemic, but to do so, will likely need to induce broadly neutralizing antibody (bnAb) responses. A major technical hurdle toward achieving this goal has been a shortage of animal models with the ability to systematically pinpoint roadblocks to bnAb induction and to rank vaccine strategies based on their ability to stimulate bnAb development. Over the past 6 years, immunoglobulin (Ig) knock-in (KI) technology has been leveraged to express bnAbs in mice, an approach that has enabled elucidation of various B-cell tolerance mechanisms limiting bnAb production and evaluation of strategies to circumvent such processes. From these studies, in conjunction with the wealth of information recently obtained regarding the evolutionary pathways and paratopes/epitopes of multiple bnAbs, it has become clear that the very features of bnAbs desired for their function will be problematic to elicit by traditional vaccine paradigms, necessitating more iterative testing of new vaccine concepts. To meet this need, novel bnAb KI models have now been engineered to express either inferred prerearranged V(D)J exons (or unrearranged germline V, D, or J segments that can be assembled into functional rearranged V(D)J exons) encoding predecessors of mature bnAbs. One encouraging approach that has materialized from studies using such newer models is sequential administration of immunogens designed to bind progressively more mature bnAb predecessors. In this review, insights into the regulation and induction of bnAbs based on the use of KI models will be discussed, as will new Ig KI approaches for higher-throughput production and/or altering expression of bnAbs in vivo, so as to further enable vaccine-guided bnAb induction studies.

      PubDate: 2017-04-14T04:09:22Z
  • Tissue-Specific Diversity and Functions of Conventional Dendritic Cells
    • Authors: Dalia Pakalniškytė; Barbara U. Schraml
      Abstract: Publication date: Available online 27 March 2017
      Source:Advances in Immunology
      Author(s): Dalia Pakalniškytė, Barbara U. Schraml
      Dendritic cells (DCs) are versatile controllers of immunity, which sense infection or tissue damage and, accordingly, initiate innate and adaptive effector responses. In recent years, it has become evident that DCs exist as an independent hematopoietic lineage comprising several developmentally distinct and functionally specialized subsets that are strategically located in all organs to defend the organism against invading pathogens. Here, we review the diversity of DC subtypes found across tissues and discuss our current understanding of the tissue-specific functions of these cell types.

      PubDate: 2017-03-30T18:45:04Z
      DOI: 10.1016/
  • A Mechanistic Understanding of Pyroptosis: The Fiery Death Triggered by
           Invasive Infection
    • Authors: Xing Liu; Judy Lieberman
      Abstract: Publication date: Available online 24 March 2017
      Source:Advances in Immunology
      Author(s): Xing Liu, Judy Lieberman
      Immune cells and skin and mucosal epithelial cells recognize invasive microbes and other signs of danger to sound alarms that recruit responder cells and initiate an immediate “innate” immune response. An especially powerful alarm is triggered by cytosolic sensors of invasive infection that assemble into multimolecular complexes, called inflammasomes, that activate the inflammatory caspases, leading to maturation and secretion of proinflammatory cytokines and pyroptosis, an inflammatory death of the infected cell. Work in the past year has defined the molecular basis of pyroptosis. Activated inflammatory caspases cleave Gasdermin D (GSDMD), a cytosolic protein in immune antigen-presenting cells and epithelia. Cleavage separates the autoinhibitory C-terminal fragment from the active N-terminal fragment, which moves to the cell membrane, binds to lipids on the inside of the cell membrane, and oligomerizes to form membrane pores that disrupt cell membrane integrity, causing death and leakage of small molecules, including the proinflammatory cytokines and GSDMD itself. GSDMD also binds to cardiolipin on bacterial membranes and kills the very bacteria that activate the inflammasome. GSDMD belongs to a family of poorly studied gasdermins, expressed in the skin and mucosa, which can also form membrane pores. Spontaneous mutations that disrupt the binding of the N- and C-terminal domains of other gasdermins are associated with alopecia and asthma. Here, we review recent studies that identified the roles of the inflammasome, inflammatory caspases, and GSDMD in pyroptosis and highlight some of the outstanding questions about their roles in innate immunity, control of infection, and sepsis.

      PubDate: 2017-03-24T18:25:08Z
      DOI: 10.1016/
  • A Chemoattractant-Guided Walk Through Lymphopoiesis: From Hematopoietic
           Stem Cells to Mature B Lymphocytes
    • Authors: Vivian Y. Lim; Sandra Zehentmeier; Chris Fistonich; João P. Pereira
      Abstract: Publication date: Available online 18 March 2017
      Source:Advances in Immunology
      Author(s): Vivian Y. Lim, Sandra Zehentmeier, Chris Fistonich, João P. Pereira
      B lymphocytes develop from hematopoietic stem cells (HSCs) in specialized bone marrow niches composed of rare mesenchymal lineage stem/progenitor cells (MSPCs) and sinusoidal endothelial cells. These niches are defined by function and location: MSPCs are mostly perisinusoidal cells that together with a small subset of sinusoidal endothelial cells express stem cell factor, interleukin-7 (IL-7), IL-15, and the highest amounts of CXCL12 in bone marrow. Though rare, MSPCs are morphologically heterogeneous, highly reticular, and form a vast cellular network in the bone marrow parenchyma capable of interacting with large numbers of hematopoietic cells. HSCs, downstream multipotent progenitor cells, and common lymphoid progenitor cells utilize CXCR4 to fine-tune access to critical short-range growth factors provided by MSPCs for their long-term maintenance and/or multilineage differentiation. In later stages, developing B lymphocytes use CXCR4 to navigate the bone marrow parenchyma, and predominantly cannabinoid receptor-2 for positioning within bone marrow sinusoids, prior to being released into peripheral blood circulation. In the final stages of differentiation, transitional B cells migrate to the spleen where they preferentially undergo further rounds of differentiation until selection into the mature B cell pool occurs. This bottleneck purges up to 97% of all developing B cells in a peripheral selection process that is heavily controlled not only by the intensity of BCR signaling and access to BAFF but also by the proper functioning of the B cell motility machinery.

      PubDate: 2017-03-24T18:25:08Z
      DOI: 10.1016/
  • Series Page
    • Abstract: Publication date: 2017
      Source:Advances in Immunology, Volume 133

      PubDate: 2017-02-21T13:28:16Z
  • γδ T Cells and B Cells
    • Authors: Willi K. Born; Yafei Huang; R. Lee Reinhardt; Hua Huang; Deming Sun; Rebecca L. O’Brien
      Abstract: Publication date: Available online 14 February 2017
      Source:Advances in Immunology
      Author(s): Willi K. Born, Yafei Huang, R. Lee Reinhardt, Hua Huang, Deming Sun, Rebecca L. O’Brien
      γδ T cells constitute the third arm of a tripartite adaptive immune system in jawed vertebrates, besides αβ T cells and B cells. Like the other two lymphocyte-types, they express diverse antigen receptors, capable of specific ligand recognition. Functionally, γδ T cells represent a system of differentiated subsets, sometimes engaged in cross-regulation, which ultimately determines their effect on other components of the immune system, including B cells and antibodies. γδ T cells are capable of providing help to B cells in antibody production. More recently it became clear that γδ T cells influence B cell differentiation during the peripheral stages of B cell development, control levels of circulating immunoglobulin (all subclasses), and affect production of autoantibodies. Because of this relationship between γδ T cells and B cells, the extensive variation of γδ T cells among human individuals might be expected to modulate their humoral responsiveness.

      PubDate: 2017-02-14T21:03:04Z
      DOI: 10.1016/
  • Regulation of Innate and Adaptive Immunity by TGFβ
    • Authors: Aoife Kelly; Stephanie A. Houston; Eleanor Sherwood; Joshua Casulli; Mark A. Travis
      Abstract: Publication date: Available online 10 February 2017
      Source:Advances in Immunology
      Author(s): Aoife Kelly, Stephanie A. Houston, Eleanor Sherwood, Joshua Casulli, Mark A. Travis
      Immune regulation by cytokines is crucial in maintaining immune homeostasis, promoting responses to infection, resolving inflammation, and promoting immunological memory. Additionally, cytokine responses drive pathology in immune-mediated disease. A crucial cytokine in the regulation of all aspects of an immune response is transforming growth factor beta (TGFβ). Although best known as a crucial regulator of T cell responses, TGFβ plays a vital role in regulating responses mediated by virtually every innate and adaptive immune cell, including dendritic cells, B cells, NK cells, innate lymphoid cells, and granulocytes. Here, we review our current knowledge of how TGFβ regulates the immune system, highlighting the multifunctional nature of TGFβ and how its function can change depending on location and context of action.

      PubDate: 2017-02-14T21:03:04Z
      DOI: 10.1016/
  • Macrophages and Mitochondria: A Critical Interplay Between Metabolism,
           Signaling, and the Functional Activity
    • Authors: J. Tur; T. Vico; J. Lloberas; A. Zorzano; A. Celada
      Abstract: Publication date: Available online 4 January 2017
      Source:Advances in Immunology
      Author(s): J. Tur, T. Vico, J. Lloberas, A. Zorzano, A. Celada
      Macrophages are phagocytic cells that participate in a broad range of cellular functions and they are key regulators of innate immune responses and inflammation. Mitochondria are highly dynamic endosymbiotic organelles that play key roles in cellular metabolism and apoptosis. Mounting evidence suggests that mitochondria are involved in the interplay between metabolism and innate immune responses. The ability of these organelles to alter the metabolic profile of a cell, thereby allowing an appropriate response to each situation, is crucial for the correct establishment of immune responses. Furthermore, mitochondria act as scaffolds for many proteins involved in immune signaling pathways and as such they are able to modulate the function of these proteins. Finally, mitochondria release molecules, such as reactive oxygen species, which directly regulate the immune response. In summary, mitochondria can be considered as core components in the regulation of innate immune signaling. Here we discuss the intricate relationship between mitochondria, metabolism, intracellular signaling, and innate immune responses in macrophages.

      PubDate: 2017-01-12T16:34:01Z
      DOI: 10.1016/
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