Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation.
Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation.
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DOI：
10.1038/ncomms1311
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发表时间：
2011
影响因子：
16.6
通讯作者：
Xiong, Huabao
中科院分区：
文献类型：
--
作者：
Ouyang, Xinshou;Zhang, Ruihua;Yang, Jianjun;Li, Qingshan;Qin, Lihui;Zhu, Chen;Liu, Jianguo;Ning, Huan;Shin, Min Sun;Gupta, Monica;Qi, Chen-Feng;He, John Cijiang;Lira, Sergio A.;Morse, Herbert C., III;Ozato, Keiko;Mayer, Lloyd;Xiong, Huabao
Th17细胞被认为是T辅助细胞的一个独特亚群，在自身免疫和组织炎症的发病机制中起着关键作用。虽然RoRγt对于Th17细胞的产生是必需的，但其功能多样性的分子机制尚不完全清楚。在这里，我们证明了干扰素调节因子(IRF)转录因子家族的成员IRF8在沉默TH17细胞分化中起着关键作用。具有传统的IRF8基因敲除和T细胞特异性缺失的小鼠表现出更有效的TH17细胞。事实上，对实验性结肠炎模型的研究表明，IRF8缺乏会导致更严重的炎症，并带有增强的TH17表型。在Th17细胞分化的过程中，IRF8被稳定地诱导并抑制其分化，至少部分是通过它与RoRγt的物理相互作用。这些发现将其定义为一种新的Th17细胞分化的内在转录抑制因子。调控TH17细胞多样性的分子机制知之甚少。欧阳等人。显示转录因子干扰素调节因子-8是TH17细胞分化所必需的，并且它的缺失增加了实验性结肠炎模型的严重性。
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. The molecular mechanisms that regulate TH17 cell diversity are poorly understood. Ouyang et al. show that the transcription factor interferon regulatory factor-8 is required for TH17-cell differentiation and that its absence increases the severity of an experimental model of colitis.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
4.4
作者：
Marecki, S;Riendeau, CJ;Fenton, MJ
通讯作者：
Fenton, MJ
DOI：
10.1084/jem.20080218
发表时间：
2008-07-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ma CS;Chew GY;Simpson N;Priyadarshi A;Wong M;Grimbacher B;Fulcher DA;Tangye SG;Cook MC
通讯作者：
Cook MC
影响因子：
3.1
作者：
BARBER, SA;FULTZ, MJ;VOGEL, SN
通讯作者：
VOGEL, SN