title: Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation.
abstract: T(H)17 cells are recognized as a unique subset of T helper cells that have critical roles in the pathogenesis of autoimmunity and tissue inflammation. Although RORγt is necessary for the generation of T(H)17 cells, the molecular mechanisms underlying the functional diversity of T(H)17 cells are not fully understood. Here we show that a member of interferon regulatory factor (IRF) family of transcription factors, IRF8, has a critical role in silencing T(H)17-cell differentiation. Mice with a conventional knockout, as well as a T cell-specific deletion, of the Irf8 gene exhibited more efficient T(H)17 cells. Indeed, studies of an experimental model of colitis showed that IRF8 deficiency resulted in more severe inflammation with an enhanced T(H)17 phenotype. IRF8 was induced steadily and inhibited T(H)17-cell differentiation during T(H)17 lineage commitment at least in part through its physical interaction with RORγt. These findings define IRF8 as a novel intrinsic transcriptional inhibitor of T(H)17-cell differentiation.
authors.affiliation: Immunology Institute, Department of Medicine, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, New York 10029, USA.
authors.forename: Xinshou
authors.initials: X
authors.lastname: Ouyang
authors.forename: Ruihua
authors.initials: R
authors.lastname: Zhang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yang
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Li
authors.forename: Lihui
authors.initials: L
authors.lastname: Qin
authors.forename: Chen
authors.initials: C
authors.lastname: Zhu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Liu
authors.forename: Huan
authors.initials: H
authors.lastname: Ning
authors.forename: Min Sun
authors.initials: MS
authors.lastname: Shin
authors.forename: Monica
authors.initials: M
authors.lastname: Gupta
authors.forename: Chen-Feng
authors.initials: CF
authors.lastname: Qi
authors.forename: John Cijiang
authors.initials: JC
authors.lastname: He
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lira
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
authors.forename: Keiko
authors.initials: K
authors.lastname: Ozato
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mayer
authors.forename: Huabao
authors.initials: H
authors.lastname: Xiong
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D005260:Female; D020868:Gene Silencing; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017384:Sequence Deletion; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology; D000099185:Interferon Regulatory Factor-8
chemical_list: D050835:Interferon Regulatory Factors; D020381:Interleukin-17; D000099185:Interferon Regulatory Factor-8