Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells

Immunity. 2021 Apr 13;54(4):702-720.e17. doi: 10.1016/j.immuni.2021.03.007. Epub 2021 Mar 30.


Murine regulatory T (Treg) cells in tissues promote tissue homeostasis and regeneration. We sought to identify features that characterize human Treg cells with these functions in healthy tissues. Single-cell chromatin accessibility profiles of murine and human tissue Treg cells defined a conserved, microbiota-independent tissue-repair Treg signature with a prevailing footprint of the transcription factor BATF. This signature, combined with gene expression profiling and TCR fate mapping, identified a population of tissue-like Treg cells in human peripheral blood that expressed BATF, chemokine receptor CCR8 and HLA-DR. Human BATF+CCR8+ Treg cells from normal skin and adipose tissue shared features with nonlymphoid T follicular helper-like (Tfh-like) cells, and induction of a Tfh-like differentiation program in naive human Treg cells partially recapitulated tissue Treg regenerative characteristics, including wound healing potential. Human BATF+CCR8+ Treg cells from healthy tissue share features with tumor-resident Treg cells, highlighting the importance of understanding the context-specific functions of these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Basic-Leucine Zipper Transcription Factors / immunology
  • Cell Differentiation / immunology
  • Cell Line
  • Chromatin / immunology*
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / immunology
  • HaCaT Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Receptors, CCR8 / immunology
  • T Follicular Helper Cells / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Wound Healing / immunology*


  • Basic-Leucine Zipper Transcription Factors
  • Chromatin
  • Receptors, CCR8