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
Department of Rheumatology and Immunology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230021, China.
Department of Rheumatology and Immunology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230021, China; Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, Anhui 230088, China.
Cell Rep. 2022 Nov 8;41(6):111606. doi: 10.1016/j.celrep.2022.111606.
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 CCR7CD74 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.
系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，已知CD4 T细胞会促进SLE的发展。在此，我们通过对72例SLE患者和30例健康对照的外周CD4 T细胞进行转座酶可及染色质高通量测序（ATAC-seq）和单细胞转录组测序（单细胞RNA测序[scRNA-seq]），探索CD4 T细胞调控组的异质性及其与SLE发病机制的关联。CD4 T细胞的染色质可及性特征与疾病严重程度相关。此外，我们生成了健康和SLE CD4 T细胞的34176个单细胞转录组，并揭示了调节性T（Treg）细胞的转录功能障碍，确定了两个Treg亚群，其中CCR7CD74 Treg亚组在SLE患者中表现出I型干扰素诱导的功能耗竭。这些关于SLE Treg的转录组水平发现反映在ATAC-seq数据的趋势中。我们的研究为理解SLE建立了丰富的实证基础，并揭示了具有耗竭样特性的Treg对SLE发病机制此前未知的贡献。
