@article{6fb7659f5eb14b57a7abf1894f84072b,
title = "Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation",
abstract = "TH17 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 H17 cells, the molecular mechanisms underlying the functional diversity of TH17 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 TH17-cell differentiation. Mice with a conventional knockout, as well as a T cell-specific deletion, of the Irf8 gene exhibited more efficient TH17 cells. Indeed, studies of an experimental model of colitis showed that IRF8 deficiency resulted in more severe inflammation with an enhanced TH17 phenotype. IRF8 was induced steadily and inhibited TH17-cell differentiation during T H17 lineage commitment at least in part through its physical interaction with RORγt. These findings define IRF8 as a novel intrinsic transcriptional inhibitor of TH17-cell differentiation.",
author = "Xinshou Ouyang and Ruihua Zhang and Jianjun Yang and Qingshan Li and Lihui Qin and Chen Zhu and Jianguo Liu and Huan Ning and Shin, {Min Sun} and Monica Gupta and Qi, {Chen Feng} and He, {John Cijiang} and Lira, {Sergio A.} and Morse, {Herbert C.} and Keiko Ozato and Lloyd Mayer and Huabao Xiong",
note = "Funding Information: We thank C. Dong, A. Yoshimura, T. Taniguchi, O. Sakaguchi, M. Ono, H. Wang, J. Yang and G. Lu for providing reagents, technical supports and helpful suggestions. We are grateful to J. Unkeless, K. Honda and J. Blander for critical reading of the manuscript. This work was supported by the NIH P01 DK072201, a Crohn{\textquoteright}s and Colitis Foundation of America grant, a grant from the Eli and Edythe L. Broad Foundation, and by the intramural research programme of the NIH, National Institute of Allergy and Infectious Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.",
year = "2011",
doi = "10.1038/ncomms1311",
language = "English",
volume = "2",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}