Journal ArticleDOI
The adaptor Act1 is required for interleukin 17–dependent signaling associated with autoimmune and inflammatory disease
Youcun Qian,Caini Liu,Justin Hartupee,Cengiz Z. Altuntas,Muhammet F. Gulen,Daniel Jane-wit,Jianhua Xiao,Yi Lu,Natalia Giltiay,Jinbo Liu,Tomasz Kordula,Qi-Wei Zhang,Bruce A. Vallance,Shadi Swaidani,Mark A. Aronica,Vincent K. Tuohy,Thomas A. Hamilton,Xiaoxia Li +17 more
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TLDR
The data show that Act1 is essential in IL-17-dependent signaling in autoimmune and inflammatory disease and was associated with much less inflammatory disease in vivo in both autoimmune encephalomyelitis and dextran sodium sulfate–induced colitis.Abstract:
T helper cells that produce interleukin 17 (IL-17) are associated with inflammation and the control of certain bacteria. We report here the essential involvement of the adaptor protein Act1 in IL-17 receptor (IL-17R) signaling and IL-17-dependent immune responses. After stimulation with IL-17, recruitment of Act1 to IL-17R required the IL-17R conserved cytoplasmic 'SEFIR' domain, followed by recruitment of the kinase TAK1 and E3 ubiquitin ligase TRAF6, which mediate 'downstream' activation of transcription factor NF-kappaB. IL-17-induced expression of inflammation-related genes was abolished in Act1-deficient primary astroglial and gut epithelial cells. This reduction was associated with much less inflammatory disease in vivo in both autoimmune encephalomyelitis and dextran sodium sulfate-induced colitis. Our data show that Act1 is essential in IL-17-dependent signaling in autoimmune and inflammatory disease.read more
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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
The Biological Functions of T Helper 17 Cell Effector Cytokines in Inflammation
TL;DR: The effector cytokines of Th17 cells mediate the crucial crosstalk between immune system and tissues, and play indispensable roles in tissue immunity.
Journal ArticleDOI
Structure and signalling in the IL-17 receptor family.
TL;DR: Research defining the signal transduction pathways induced by IL-17R family cytokines has lagged behind that of other cytokine families, but studies in the past 2 years have begun to delineate unusual functional motifs and new proximal signalling mediators used by the IL- 17R family to mediate downstream events.
Journal ArticleDOI
The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing
TL;DR: This Review focuses on the recent advances that have been made regarding the transcriptional control of TH 17 cell plasticity and stability, as well as the effector functions of TH17 cells, and highlights the mechanisms of IL-17 signalling in mesenchymal and barrier epithelial tissues.
Journal ArticleDOI
Targeting IL-17 and TH17 cells in chronic inflammation.
Pierre Miossec,Jay K. Kolls +1 more
TL;DR: This Review focuses on the current knowledge of the IL-17–TH17 cell pathway to better understand the positive as well as potential negative consequences of targeting them.
References
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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.