Title: Regulatory T Cell-Specific Epigenomic Region Variants Are a Key Determinant of Susceptibility to Common Autoimmune Diseases
Author: Naganari Ohkura, Yoshiaki Yasumizu, Yohko Kitagawa, Atsushi Tanaka, Yamami Nakamura, Daisuke Motooka, Shota Nakamura, Yukinori Okada, Shimon Sakaguchi
Abstract: The contribution of FOXP3-expressing naturally occurring regulatory T (Treg) cells to common polygenic autoimmune diseases remains ambiguous. Here, we characterizedgenome-wide epigenetic profiles (CpG methylation and histone modifications) of humanTreg and conventional T (Tconv) cells in naive and activated states. We found thatsingle-nucleotide polymorphisms (SNPs) associated with common autoimmune diseaseswere predominantly enriched in CpG demethylated regions (DRs) specifically presentin naive Treg cells but much less enriched in activation-induced DRs common in Tconvand Treg cells. Naive Treg cell-specific DRs were largely included in Treg cell-specificsuper-enhancers and closely associated with transcription and other epigenetic changesin naive and effector Treg cells. Thus, naive Treg cell-specific CpG hypomethylationhad a key role in controlling Treg cell-specific gene transcription and epigeneticmodification. The results suggest possible contribution of altered function or developmentof natural Treg cells to the susceptibility to common autoimmune diseases.