Journal ArticleDOI
Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system.
Jason S. Stumhofer,Arian Laurence,Emma H. Wilson,Elaine Huang,Cristina M. Tato,Leanne M. Johnson,Alejandro V. Villarino,Qiulong Huang,Akihiko Yoshimura,David Sehy,Christiaan J. M. Saris,John J. O'Shea,Lothar Hennighausen,Matthias Ernst,Christopher A. Hunter +14 more
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TLDR
It is shown that IL-27 receptor–deficient mice chronically infected with Toxoplasma gondii developed severe neuroinflammation that was CD4+ T cell dependent and was associated with a prominent IL-17 response.Abstract:
Studies have focused on the events that influence the development of interleukin 17 (IL-17)–producing T helper cells (TH-17 cells) associated with autoimmunity, such as experimental autoimmune encephalitis, but relatively little is known about the cytokines that antagonize TH-17 cell effector responses. Here we show that IL-27 receptor–deficient mice chronically infected with Toxoplasma gondii developed severe neuroinflammation that was CD4+ T cell dependent and was associated with a prominent IL-17 response. In vitro, treatment of naive primary T cells with IL-27 suppressed the development TH-17 cells induced by IL-6 and transforming growth factor-β, which was dependent on the intracellular signaling molecule STAT1 but was independent of inhibition of IL-6 signaling mediated by the suppressor protein SOCS3. Thus IL-27, a potent inhibitor of TH-17 cell development, may be a useful target for treating inflammatory diseases mediated by these cells.read more
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IL-17 and Th17 Cells.
TL;DR: The investigation of the differentiation, effector function, and regulation of Th17 cells has opened up a new framework for understanding T cell differentiation and now appreciate the importance of Th 17 cells in clearing pathogens during host defense reactions and in inducing tissue inflammation in autoimmune disease.
Journal ArticleDOI
IL-6 in Inflammation, Immunity, and Disease
TL;DR: The mechanism for the continual synthesis of IL-6 needs to be elucidated to facilitate the development of more specific therapeutic approaches and analysis of the pathogenesis of specific diseases.
Journal ArticleDOI
Cytokines in the pathogenesis of rheumatoid arthritis
Iain B. McInnes,Georg Schett +1 more
TL;DR: The crucial effector function of cytokines in the immunological processes that are central to the pathogenesis of rheumatoid arthritis are discussed.
Journal ArticleDOI
IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways.
Liang Zhou,Ivaylo I. Ivanov,Rosanne Spolski,Roy Min,Kevin Shenderov,Takeshi Egawa,David E. Levy,Warren J. Leonard,Dan R. Littman +8 more
TL;DR: IL-6 orchestrates a series of 'downstream' cytokine-dependent signaling pathways that, in concert with TGF-β, amplify RORγt-dependent differentiation of TH-17 cells.
Journal ArticleDOI
Development, cytokine profile and function of human interleukin 17-producing helper T cells
Nicholas J. Wilson,Katia Boniface,Jason R. Chan,Brent S. McKenzie,Wendy M. Blumenschein,Jeanine D. Mattson,Beth Basham,Kathleen M. Smith,Taiying Chen,Franck Morel,Jean-Claude Lecron,Robert A. Kastelein,Daniel J. Cua,Terrill K. McClanahan,Edward P. Bowman,Rene de Waal Malefyt +15 more
TL;DR: It is demonstrated that IL-23 and IL-1β induced the development of human and mouse TH-17 cells expressing IL-17A,IL-17F, IL-22, Il-26, interferon-γ, the chemokine CCL20 and transcription factor RORγt, and that human TH- 17 cells may regulate innate immunity in epithelial cells.
References
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Journal ArticleDOI
TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties.
Tim R. Mosmann,R L Coffman +1 more
TL;DR: Two types of cloned helper T cells are described, defined primarily by differences in the pattern of lymphokines ynthesized, and the different functions of the two types of cells and their lymphokine synthesis are discussed.
Journal ArticleDOI
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells.
Estelle Bettelli,Yijun Carrier,Wenda Gao,Thomas Korn,Terry B. Strom,Mohamed Oukka,Howard L. Weiner,Vijay K. Kuchroo +7 more
TL;DR: It is shown that IL-6, an acute phase protein induced during inflammation, completely inhibits the generation of Foxp3+ Treg cells induced by TGF-β, and the data demonstrate a dichotomy in thegeneration of pathogenic (TH17) T cells that induce autoimmunity and regulatory (Foxp3+) T Cells that inhibit autoimmune tissue injury.
Journal ArticleDOI
Interleukin 17–producing CD4 + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
Laurie E. Harrington,Robin D. Hatton,Paul R. Mangan,Henrietta Turner,Theresa L. Murphy,Kenneth M. Murphy,Casey T. Weaver +6 more
TL;DR: Findings provide a basis for understanding how inhibition of IFN-γ signaling enhances development of pathogenic TH-17 effector cells that can exacerbate autoimmunity.
Journal ArticleDOI
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Heon Park,Zhaoxia Li,Xuexian O. Yang,Seon Hee Chang,Roza Nurieva,Yi Hong Wang,Ying Wang,Leroy Hood,Zhou Zhu,Qiang Tian,Chen Dong +10 more
TL;DR: In vivo, antibody to IL- 17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused Chemokine production and leukocyte infiltration, indicating a unique T helper lineage that regulates tissue inflammation.
Journal ArticleDOI
IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
Claire L. Langrish,Yi Yi Chen,Wendy M. Blumenschein,Jeanine D. Mattson,Beth Basham,Jonathan D. Sedgwick,Terrill K. McClanahan,Robert A. Kastelein,Daniel J. Cua +8 more
TL;DR: Using passive transfer studies, it is confirmed that these IL-23–dependent CD4+ T cells are highly pathogenic and essential for the establishment of organ-specific inflammation associated with central nervous system autoimmunity.