In Cell reports ; h5-index 119.0
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and CD4+ T cells are known to promote SLE development. Here, we explore heterogeneities in the CD4+ T cell regulome and their associations with SLE pathogenesis by performing assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and single-cell transcriptome sequencing (single-cell RNA sequencing [scRNA-seq]) of peripheral CD4+ T cells from 72 SLE patients and 30 healthy controls. Chromatin accessibility signatures of CD4+ T cells are correlated with disease severity. Further, we generate 34,176 single-cell transcriptomes of healthy and SLE CD4+ T cells and reveal transcriptional dysfunction of regulatory T (Treg) cells, identifying two Treg subpopulations, among which the CCR7lowCD74hi Treg subgroup features type I interferon-induced functional exhaustion in SLE patients. These transcriptome-level findings for SLE Tregs are mirrored in trends from the ATAC-seq data. Our study establishes a rich empirical foundation for understanding SLE and uncovers previously unknown contributions of Treg with exhaustion-like properties to SLE pathogenesis.
Guo Chuang, Liu Qian, Zong Dandan, Zhang Wen, Zuo Zuqi, Yu Qiaoni, Sha Qing, Zhu Lin, Gao Xuyuan, Fang Jingwen, Tao Jinhui, Wu Quan, Li Xiaomei, Qu Kun
2022-Nov-08
ATAC-seq, CD4(+) T cells, CP: Immunology, SLE, Treg exhaustion, scRNA-seq, type I interferon
