The epigenetic regulator ATF7ip inhibits Il2 expression, regulating Th17 responses.
The epigenetic regulator ATF7ip inhibits Il2 expression, regulating Th17 responses.
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表观遗传调节因子 ATF7ip 抑制 Il2 表达，调节 Th17 反应。
DOI：
10.1084/jem.20182316
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Waterfield,MichaelR
中科院分区：
文献类型：
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作者：
Sin,JunHyung;Zuckerman,Cassandra;Cortez,JessicaT;Eckalbar,WalterL;Erle,DavidJ;Anderson,MarkS;Waterfield,MichaelR
辅助性T - 17细胞（Th17）对抵抗粘膜表面感染至关重要；然而，它们也被发现与多种自身免疫性疾病的发病机制有关，并已被用于靶向治疗。由于Th17细胞在自身免疫发病机制中的作用，了解控制Th17发展的因素非常重要。在这里，我们发现激活转录因子7相互作用蛋白（ATF7ip）是Th17分化的关键调节因子。T细胞特异性缺失atf7ipd的小鼠在T细胞受体（TCR）刺激下继发于IL-2异常过量产生的Th17分化受损，并且在体内对结肠炎具有抗性。ChIP-seq研究发现，ATF7ip通过抑制组蛋白标记H3K9me3沉积在il2 - il21基因间区，抑制了ofil2基因的表达。这些结果证明了一种新的表观遗传途径，IL-2的产生受到限制，这可能为调节IL-2的产生开辟新的途径。
T helper 17 cells (Th17) are critical for fighting infections at mucosal surfaces; however, they have also been found to contribute to the pathogenesis of multiple autoimmune diseases and have been targeted therapeutically. Due to the role of Th17 cells in autoimmune pathogenesis, it is important to understand the factors that control Th17 development. Here we identify the activating transcription factor 7 interacting protein (ATF7ip) as a critical regulator of Th17 differentiation. Mice with T cell–specific deletion ofAtf7iphave impaired Th17 differentiation secondary to the aberrant overproduction of IL-2 with T cell receptor (TCR) stimulation and are resistant to colitis in vivo. ChIP-seq studies identified ATF7ip as an inhibitor ofIl2gene expression through the deposition of the repressive histone mark H3K9me3 in theIl2-Il21intergenic region. These results demonstrate a new epigenetic pathway by which IL-2 production is constrained, and this may open up new avenues for modulating its production.