Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation.

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2011

Nat Commun 2011;2:314. doi: 10.1038/ncomms1311.

Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation.

Gupta, M;He, JC;Li, Q;Lira, SA;Liu, J;Mayer, L;Morse, HC 3rd;Ning, H;Ouyang, X;Ozato, K;Qi, CF;Qin, L;Shin, MS;Xiong, H.;Yang, J;Zhang, R;Zhu, C

Immunology Institute, Department of Medicine, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, New York 10029, USA.

Service type: Knock-in mice

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 TH17 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 TH17 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.

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