Single-cell transcriptome profiling and chromatin accessibility reveal an exhausted regulatory CD4+ T cell subset in systemic lupus erythematosus.
Cell Rep
; 41(6): 111606, 2022 11 08.
Article
em En
| MEDLINE
| ID: mdl-36351407
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Reguladores
/
Lúpus Eritematoso Sistêmico
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article