Journal ArticleDOI
Interleukin-22, a T H 17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis
Yan Zheng,Dimitry M. Danilenko,Patricia Valdez,Ian Kasman,Jeffrey Eastham-Anderson,Jianfeng Wu,Wenjun Ouyang +6 more
Reads0
Chats0
TLDR
The results suggest that TH17 cells, through the production of both IL-22 and IL-17, might have essential functions in host defence and in the pathogenesis of autoimmune diseases such as psoriasis.Abstract:
Psoriasis is a chronic inflammatory skin disease characterized by hyperplasia of the epidermis (acanthosis), infiltration of leukocytes into both the dermis and epidermis, and dilation and growth of blood vessels. The underlying cause of the epidermal acanthosis in psoriasis is still largely unknown. Recently, interleukin (IL)-23, a cytokine involved in the development of IL-17-producing T helper cells (T(H)17 cells), was found to have a potential function in the pathogenesis of psoriasis. Here we show that IL-22 is preferentially produced by T(H)17 cells and mediates the acanthosis induced by IL-23. We found that IL-23 or IL-6 can directly induce the production of IL-22 from both murine and human naive T cells. However, the production of IL-22 and IL-17 from T(H)17 cells is differentially regulated. Transforming growth factor-beta, although crucial for IL-17 production, actually inhibits IL-22 production. Furthermore, IL-22 mediates IL-23-induced acanthosis and dermal inflammation through the activation of Stat3 (signal transduction and activators of transcription 3) in vivo. Our results suggest that T(H)17 cells, through the production of both IL-22 and IL-17, might have essential functions in host defence and in the pathogenesis of autoimmune diseases such as psoriasis. IL-22, as an effector cytokine produced by T cells, mediates the crosstalk between the immune system and epithelial cells.read more
Citations
More filters
Journal ArticleDOI
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
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
Mechanisms of Disease: Psoriasis.
TL;DR: Anti-TNF strategies have three variants: a humanized chimeric anti–TNF- α monoclonal antibody, a fully human monocolonal anti-T NF- α antibody, and a human p75 TNF-receptor Fc fusion protein.
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
More filters
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
TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-Producing T cells
Marc Veldhoen,Richard J. Hocking,Christopher J. Atkins,Richard M. Locksley,Brigitta Stockinger +4 more
TL;DR: The data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation ofIL-17-producing T cells.
Journal ArticleDOI
Transforming growth factor-beta induces development of the T(H)17 lineage.
Paul R. Mangan,Laurie E. Harrington,Darrell B. O'Quinn,Whitney S. Helms,Daniel C. Bullard,Charles O. Elson,Robin D. Hatton,Sharon M. Wahl,Trenton R. Schoeb,Casey T. Weaver +9 more
TL;DR: This article identified transforming growth factor-beta (TGF-beta) as a cytokine critical for commitment to Thelper-17 (T(H)17) development, which is required for host protection against a bacterial pathogen, Citrobacter rodentium.