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. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Michael Delacher, Malte Simon, Lieke Sanderink, Agnes Hotz-Wagenblatt, Marina Wuttke, Kathrin Schambeck, Lisa Schmidleithner, Sebastian Bittner, Asmita Pant, Uwe Ritter, Thomas Hehlgans, Dania Riegel, Verena Schneider, Florian Kai Groeber-Becker, Andreas Eigenberger, Claudia Gebhard, Nicholas Strieder, Alexander Fischer, Michael Rehli, Petra Hoffmann, Matthias Edinger, Till Strowig, Jochen Huehn, Christian Schmidl, Jens M Werner, Lukas Prantl, Benedikt Brors, Charles D Imbusch, Markus Feuerer. Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells. Immunity. 2021 Apr 13;54(4):702-720.e17

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PMID: 33789089

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