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

: Delacher, M.; Simon, M.; Sanderink, L.; Hotz-Wagenblatt, A.; Wuttke, M.; Schambeck, K.; Schmidleithner, L.; Bittner, S.; Pant, A.; Ritter, U.; Hehlgans, T.; Riegel, D.; Schneider, V.; Groeber-Becker, F.K.; Eigenberger, A.; Gebhard, C.; Strieder, N.; Fischer, A.; Rehli, M.; Hoffmann, P.; Edinger, M.; Strowig, T.; Huehn, J.; Schmidl, C.; Werner, J.M.; Prantl, L.; Brors, B.; Imbusch, C.D.; Feuerer, M.

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Immunity 54 (2021), No.4, pp.702-720.e17
ISSN: 1074-7613
ISSN: 1097-4180
Journal Article, Electronic Publication
Fraunhofer ISC ()

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.