Ouyang, XinshouZhang, RuihuaYang, JianjunLi, QingshanQin, LihuiLiu, JianguoNing, HuanShin, Min SunGupta, MonicaQi, Chen-FengLira, Sergio A.Morse, Herbert C.Ozato, KeikoMayer, LloydXiong, HuabaoZhu, ChengHe, John Cijiang2011-12-302011Ouyang, Xinshou, Ruihua Zhang, Jianjun Yang, Qingshan Li, Lihui Qin, Chen Zhu, Jianguo Liu, et al. 2011. Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation. Nature Communications 2: 314.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:5978716T\(_H\)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.en-USJournal Article2011-12-3010.1038/ncomms1311