The contribution of FOXP3-expressing naturally occurring regulatory T (Treg) cells to common polygenic autoimmune diseases remains ambiguous. Here, we characterized genome-wide epigenetic profiles (CpG methylation and histone modifications) of human Treg and conventional T (Tconv) cells in naive and activated states. We found that single-nucleotide polymorphisms (SNPs) associated with common autoimmune diseases were predominantly enriched in CpG demethylated regions (DRs) specifically present in naive Treg cells but much less enriched in activation-induced DRs common in Tconv and Treg cells. Naive Treg cell-specific DRs were largely included in Treg cell-specific super-enhancers and closely associated with transcription and other epigenetic changes in naive and effector Treg cells. Thus, naive Treg cell-specific CpG hypomethylation had a key role in controlling Treg cell-specific gene transcription and epigenetic modification. The results suggest possible contribution of altered function or development of natural Treg cells to the susceptibility to common autoimmune diseases.

表达FOXP3的天然存在的调节性T（Treg）细胞对常见的多基因自身免疫性疾病的贡献仍然不明确。在这里，我们表征了人类Treg和传统T（Tconv）细胞在幼稚和激活状态下的全基因组表观遗传学特征（CpG甲基化和组蛋白修饰）。我们发现与常见的自身免疫性疾病相关的单核苷酸多态性（SNPs）主要富含天然Treg细胞中特有的CpG去甲基化区域（DRs），而富含Tconv和Treg细胞中常见的激活诱导DRs。幼稚Treg细胞特异的DR主要包含在Treg细胞特异的超级增强剂中，并且与幼稚Treg细胞和效应Treg细胞的转录和其他表观遗传学变化密切相关。从而，幼稚的Treg细胞特异性CpG亚甲基化在控制Treg细胞特异性基因转录和表观遗传修饰中起关键作用。结果表明，天然Treg细胞功能改变或发育对常见的自身免疫性疾病的敏感性可能有贡献。