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Beumer, N.* ; Imbusch, C.D.* ; Kaufmann, T.* ; Schmidleithner, L.* ; Gütter, K.* ; Stüve, P.* ; Marchel, H.* ; Weichenhan, D.* ; Bähr, M.* ; Ruhland, B.* ; Marini, F.* ; Sanderink, L.* ; Ritter, U.* ; Simon, M.* ; Braband, K.L.* ; Voss, M.M.* ; Helbich, S.S.* ; Mihoc, D.M.* ; Hotz-Wagenblatt, A.* ; Nassabi, H.* ; Eigenberger, A.* ; Prantl, L.* ; Gebhard, C.* ; Rehli, M.* ; Strieder, N.* ; Singh, K. ; Schmidl, C.* ; Plass, C.* ; Huehn, J.* ; Hehlgans, T.* ; Polansky, J.K.* ; Brors, B.* ; Delacher, M.* ; Feuerer, M.*

DNA hypomethylation traits define human regulatory T cells in cutaneous tissue and identify their blood recirculating counterparts.

Nat. Immunol., DOI: 10.1038/s41590-025-02210-x (2025)

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CD4⁺ regulatory T (T_reg) cells in tissues play crucial immunoregulatory and regenerative roles. Despite their importance, the epigenetics and differentiation of human tissue T_reg cells are incompletely understood. Here, we performed genome-wide DNA methylation analysis of human T_reg cells from skin and blood and integrated these data into a multiomic framework, including chromatin accessibility and gene expression. This analysis identified programs that governed the tissue adaptation of skin T_reg cells. We found that subfamilies of transposable elements represented a major constituent of the hypomethylated landscape in tissue T_reg cells. Based on T cell antigen receptor sequence and DNA hypomethylation homologies, our data indicate that blood CCR8⁺ T_reg cells contain recirculating human skin T_reg cells. Conversely, differences in chromatin accessibility and gene expression suggest a certain reversal of the tissue adaptation program during recirculation. Our findings provide insights into the biology of human tissue T_reg cells, which may help harness these cells for therapeutic purposes.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

ISSN (print) / ISBN 1529-2908

e-ISSN 1529-2916

Journal Nature Immunology

Publisher Nature Publishing Group

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)