a Institut National de la Santé et de la Recherche Médicale UMR1169 , Paris Sud University, Bicêtre Hospital , Le Kremlin-Bicêtre , France.
b Fondation de l'AP-HP pour la Recherche , Paris , France.
Epigenetics. 2018;13(5):459-472. doi: 10.1080/15592294.2018.1469893. Epub 2018 Aug 10.
IL2RA, a subunit of the high affinity receptor for interleukin-2 (IL2), plays a crucial role in immune homeostasis. Notably, IL2RA expression is induced in CD4+ T cells in response to various stimuli and is constitutive in regulatory T cells (Tregs). We selected for our study 18 CpGs located within cognate regulatory regions of the IL2RA locus and characterized their methylation in naive, regulatory, and memory CD4+ T cells. We found that 5/18 CpGs (notably CpG + 3502) show dynamic, active demethylation during the in vitro activation of naive CD4+ T cells. Demethylation of these CpGs correlates with appearance of IL2RA protein at the cell surface. We found no influence of cis located SNP alleles upon CpG methylation. Treg cells show constitutive demethylation at all studied CpGs. Methylation of 9/18 CpGs, including CpG +3502, decreases with age. Our data thus identify CpG +3502 and a few other CpGs at the IL2RA locus as coordinated epigenetic regulators of IL2RA expression in CD4+ T cells. This may contribute to unravel how the IL2RA locus can be involved in immune physiology and pathology.
白细胞介素 2 受体亚基 A（IL2RA）是白细胞介素 2（IL2）高亲和力受体的一个亚基，在免疫稳态中起着至关重要的作用。值得注意的是，IL2RA 的表达在 CD4+T 细胞中受到各种刺激的诱导，并在调节性 T 细胞（Tregs）中是组成性的。我们选择了 IL2RA 基因座内的 18 个 CpG 用于研究，这些 CpG 位于相应的调节区域，并表征了它们在幼稚、调节和记忆 CD4+T 细胞中的甲基化情况。我们发现，18 个 CpG 中有 5 个（特别是 CpG +3502）在体外激活幼稚 CD4+T 细胞时表现出动态、活跃的去甲基化。这些 CpG 的去甲基化与细胞表面 IL2RA 蛋白的出现相关。我们没有发现顺式位置的 SNP 等位基因对 CpG 甲基化有影响。Treg 细胞在所有研究的 CpG 上均表现出组成性去甲基化。包括 CpG +3502 在内的 9/18 个 CpG 的甲基化随年龄的增长而降低。因此，我们的数据确定了 IL2RA 基因座上的 CpG +3502 和其他一些 CpG 作为 CD4+T 细胞中 IL2RA 表达的协调表观遗传调节剂。这可能有助于揭示 IL2RA 基因座如何参与免疫生理学和病理学。
