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Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells.
Delacher, Michael Simon, Malte Sanderink, Lieke Hotz-Wagenblatt, Agnes Wuttke, Marina Schambeck, Kathrin Schmidleithner, Lisa Bittner, Sebastian Pant, Asmita Ritter, Uwe
Delacher, Michael
Simon, Malte
Sanderink, Lieke
Hotz-Wagenblatt, Agnes
Wuttke, Marina
Schambeck, Kathrin
Schmidleithner, Lisa
Bittner, Sebastian
Pant, Asmita
Ritter, Uwe
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2021-03-30
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Abstract
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.
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Immunity. 2021 Apr 13;54(4):702-720.e17. doi: 10.1016/j.immuni.2021.03.007. Epub 2021 Mar 30.
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en
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1097-4180
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Attribution 4.0 International