The epigenetic regulator ATF7ip inhibits Il2 expression, regulating Th17 responses.,Journal of Experimental Medicine

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The epigenetic regulator ATF7ip inhibits Il2 expression, regulating Th17 responses.
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2019-06-19 , DOI: 10.1084/jem.20182316
Jun Hyung Sin _{1,

2} , Cassandra Zuckerman _{1,

2} , Jessica T Cortez _{1,

3} , Walter L Eckalbar _{4,

5} , David J Erle _{4,

5} , Mark S Anderson _{3,

4,

6} , Michael R Waterfield _{2,

6}

Affiliation

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 of Atf7ip have 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 of Il2 gene expression through the deposition of the repressive histone mark H3K9me3 in the Il2-Il21 intergenic 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.

中文翻译：

表观遗传调节因子 ATF7ip 抑制 Il2 表达，调节 Th17 反应。

辅助 T 17 细胞 (Th17) 对于抵抗粘膜表面感染至关重要；然而，它们也被发现有助于多种自身免疫性疾病的发病机制，并已成为治疗的目标。由于 Th17 细胞在自身免疫发病机制中的作用，了解控制 Th17 发育的因素非常重要。在这里，我们确定激活转录因子 7 相互作用蛋白 (ATF7ip) 是 Th17 分化的关键调节因子。 Atf7ip T 细胞特异性缺失的小鼠因 T 细胞受体 (TCR) 刺激导致 IL-2 异常过量产生而导致 Th17 分化受损，并且在体内对结肠炎具有抵抗力。 ChIP-seq 研究通过在 Il2-Il21 基因间区域沉积抑制性组蛋白标记 H3K9me3，确定 ATF7ip 是 Il2 基因表达的抑制剂。这些结果证明了一种新的表观遗传途径，通过该途径限制 IL-2 的产生，这可能为调节其产生开辟新的途径。

更新日期：2019-09-03

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