Single-cell transcriptome profiling and chromatin accessibility reveal an exhausted regulatory CD4+ T cell subset in systemic lupus erythematosus

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 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.

Keywords: ATAC-seq; CD4(+) T cells; CP: Immunology; SLE; Treg exhaustion; scRNA-seq; type I interferon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / pathology
  • Chromatin / metabolism
  • Gene Expression Profiling
  • Humans
  • Lupus Erythematosus, Systemic*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory*


  • Chromatin