Journal Article
. 2020 May; 52(6):1119-1132.e4.
doi: 10.1016/j.immuni.2020.04.006.

Regulatory T Cell-Specific Epigenomic Region Variants Are a Key Determinant of Susceptibility to Common Autoimmune Diseases

Naganari Ohkura 1 Yoshiaki Yasumizu 2 Yohko Kitagawa 3 Atsushi Tanaka 1 Yamami Nakamura 3 Daisuke Motooka 4 Shota Nakamura 4 Yukinori Okada 5 Shimon Sakaguchi 6 
  • PMID: 32362325
  •     24 citations


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.

Keywords: CD25; CTLA-4; DNA methylation; FoxP3; SNPs; autoimmune diseases; epigenome; genetic susceptibility; regulatory T cells; super-enhancer.

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