Transcriptional regulation of the Th17 immune response by IKKα
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TLDR
IKKa associates with the il17a locus and is required in T cells for Th17-mediated CNS inflammation in vivo and is involved in the regulation of T cell reprograming in vivo.Abstract:
Th17 cells are a subset of T cells that play crucial roles in the pathogenesis of many inflammatory diseases. We report here the identification of IKKα (inhibitor of NF-κB kinase-α) as a key transcriptional regulator of the Th17 lineage. T cells expressing a nonactivatable form of IKKα were significantly compromised in their ability to produce IL-17 and to initiate neural inflammation. IKKα is present in the nuclei of resting CD4+ T cells. Upon Th17 differentiation, IKKα selectively associated with the Il17a locus, and promoted its histone H3 phosphorylation and transcriptional activation in a NF-κB–independent manner. These findings indicate that nuclear IKKα maintains the Th17 phenotype by activating the Il17a gene.read more
Citations
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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
The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.
Ivaylo I. Ivanov,Brent S. McKenzie,Liang Zhou,Carlos E. Tadokoro,Alice Lepelley,Juan J. Lafaille,Daniel J. Cua,Dan R. Littman +7 more
TL;DR: It is shown that the orphan nuclear receptor RORgammat is the key transcription factor that orchestrates the differentiation of this effector cell lineage of proinflammatory T helper cells and its potential as a therapeutic target in inflammatory diseases is highlighted.
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.
Journal ArticleDOI
Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain
Daniel J. Cua,Jonathan P Sherlock,Yi Chen,Craig A. Murphy,Barbara L. Joyce,Brian W. P. Seymour,Linda Lucian,Wayne To,Sylvia Kwan,Tatyana Churakova,Sandra Zurawski,Maria T. Wiekowski,Sergio A. Lira,Sergio A. Lira,Daniel M. Gorman,Robert A. Kastelein,Jonathon D. Sedgwick +16 more
TL;DR: It is shown that the perceived central role for IL-12 in autoimmune inflammation, specifically in the brain, has been misinterpreted and that IL-23, and not IL- 12, is the critical factor in this response.
Journal ArticleDOI
T Helper 17 Lineage Differentiation Is Programmed by Orphan Nuclear Receptors RORα and RORγ
Xuexian O. Yang,Bhanu P. Pappu,Roza Nurieva,Askar M. Akimzhanov,Hong Soon Kang,Yeonseok Chung,Li Ma,Bhavin Shah,Athanasia D. Panopoulos,Kimberly S. Schluns,Stephanie S. Watowich,Qiang Tian,Anton M. Jetten,Chen Dong +13 more
TL;DR: Th17 differentiation is directed by two lineage-specific nuclear receptors, ROR alpha and ROR gamma, and is induced by transforming growth factor-beta and interleukin-6 (IL-6), which is dependent on signal transducer and activator of transcription 3.