DNA methylation and transposable element landscapes define human regulatory T cells in tissues and identify their blood recirculating counterpart

Regulatory T cells (Treg cells) in tissues can perform immunoregulatory and tissue-regenerative functions. Despite these important tasks, human-tissue Treg cells lack understanding, specifically, the epigenetic basis of their differentiation as well as re-circulating tissue-Treg cells are incompletely understood. Here, we performed genome-wide DNA methylation analysis of human Treg cells from skin and blood and embedded this in a multi-omic epigenetic framework including chromatin accessibility and gene-expression. We thereby revealed novel epigenetic programs defining human skin Treg cell differentiation and delineated how these are present on the different epigenetic levels. We discovered that transposable elements are an integral constituent of the demethylation landscape in skin Treg cells. Based on TCR-sequencing and DNA demethylation homologies, our data unveil that blood CCR8+ Treg cells are recirculatory human tissue-Treg cells. Our data provide novel insights in human tissue-Treg biology, required to harness these cells for therapeutic avenues.

Type: Epigenetics
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD50000001022	Whole genome bisulfate sequencing using tagmentation of Tcells from skin and blood.The method improved TWGBS protocol (Weichenhan et al.), Methods Mol. Biol. 2018, vol. 1708 pp.105-122) was used	Illumina NovaSeq 6000	30

Publications	Citations
DNA hypomethylation traits define human regulatory T cells in cutaneous tissue and identify their blood recirculating counterparts. Beumer N, Imbusch CD, 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 KL, Voss MM, Helbich SS, Mihoc DM, 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 JK, Brors B, Delacher M, Feuerer M. Nat Immunol 26: 2025 1315-1328	1

Publications

Citations

DNA hypomethylation traits define human regulatory T cells in cutaneous tissue and identify their blood recirculating counterparts.
Beumer N, Imbusch CD, 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 KL, Voss MM, Helbich SS, Mihoc DM, 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 JK, Brors B, Delacher M, Feuerer M. Nat Immunol 26: 2025 1315-1328