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

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.

Automated summary

Research identified features of human tissue Treg cells with tissue repair functions, which show similarities in gene expression profiles at the single-cell level with murine cells, and shared characteristics with T follicular helper-like cells. Inducing differentiation of human Treg cells into Tfh-like cells can partially replicate the regenerative characteristics of tissue Treg cells.