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<p>CD4<sup>+</sup> regulatory T (T<sub>reg</sub>) cells in tissues play crucial immunoregulatory and regenerative roles. Despite their importance, the epigenetics and differentiation of human tissue T<sub>reg</sub> cells are incompletely understood. Here, we performed genome-wide DNA methylation analysis of human T<sub>reg</sub> 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<sub>reg</sub> cells. We found that subfamilies of transposable elements represented a major constituent of the hypomethylated landscape in tissue T<sub>reg</sub> cells. Based on T cell antigen receptor sequence and DNA hypomethylation homologies, our data indicate that blood CCR8<sup>+</sup> T<sub>reg</sub> cells contain recirculating human skin T<sub>reg</sub> 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<sub>reg</sub> cells, which may help harness these cells for therapeutic purposes.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月16日

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  • Niklas Beumer,
  • Charles D. Imbusch,
  • Tamara Kaufmann,
  • Lisa Schmidleithner,
  • Kathrin Gütter,
  • Philipp Stüve,
  • Harriet Marchel,
  • Dieter Weichenhan,
  • Marion Bähr,
  • Brigitte Ruhland,
  • Federico Marini,
  • Lieke Sanderink,
  • Uwe Ritter,
  • Malte Simon,
  • Kathrin Luise Braband,
  • Morten Michael Voss,
  • Sara Salome Helbich,
  • Delia Mihaela Mihoc,
  • Agnes Hotz-Wagenblatt,
  • Hadrian Nassabi,
  • Andreas Eigenberger,
  • Lukas Prantl,
  • Claudia Gebhard,
  • Michael Rehli,
  • Nicholas Strieder,
  • Kartikeya Singh,
  • Christian Schmidl,
  • Christoph Plass,
  • Jochen Huehn,
  • Thomas Hehlgans,
  • Julia K. Polansky,
  • Benedikt Brors,
  • Michael Delacher,
  • Markus Feuerer

摘要

CD4+ regulatory T (Treg) cells in tissues play crucial immunoregulatory and regenerative roles. Despite their importance, the epigenetics and differentiation of human tissue Treg cells are incompletely understood. Here, we performed genome-wide DNA methylation analysis of human Treg 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 Treg cells. We found that subfamilies of transposable elements represented a major constituent of the hypomethylated landscape in tissue Treg cells. Based on T cell antigen receptor sequence and DNA hypomethylation homologies, our data indicate that blood CCR8+ Treg cells contain recirculating human skin Treg 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 Treg cells, which may help harness these cells for therapeutic purposes.