Delacher, M.M.DelacherSimon, M.M.SimonSanderink, L.L.SanderinkHotz-Wagenblatt, A.A.Hotz-WagenblattWuttke, M.M.WuttkeSchambeck, K.K.SchambeckSchmidleithner, L.L.SchmidleithnerBittner, S.S.BittnerPant, A.A.PantRitter, U.U.RitterHehlgans, T.T.HehlgansRiegel, D.D.RiegelSchneider, V.V.SchneiderGroeber-Becker, F.K.F.K.Groeber-BeckerEigenberger, A.A.EigenbergerGebhard, C.C.GebhardStrieder, N.N.StriederFischer, A.A.FischerRehli, M.M.RehliHoffmann, P.P.HoffmannEdinger, M.M.EdingerStrowig, T.T.StrowigHuehn, J.J.HuehnSchmidl, C.C.SchmidlWerner, J.M.J.M.WernerPrantl, L.L.PrantlBrors, B.B.BrorsImbusch, C.D.C.D.ImbuschFeuerer, M.M.Feuerer2022-03-062022-03-062021https://publica.fraunhofer.de/handle/publica/26935510.1016/j.immuni.2021.03.007Murine 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.en666610journal article