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@ARTICLE{Fischer:306581,
      author       = {J. C. Fischer and S. Göttert and M. Giller and P. Heinrich
                      and K. Fan and O. Khalid and C. N. Walther and M. Drießlein
                      and S. M. Nefzger and G. Eisenkolb and V. R. Timnik and S.
                      Jarosch and L. Klostermeier and T. Engleitner and N.
                      Strieder and C. Gebhard and S. Diederich and N. A. Schmid
                      and L. Lansink Rotgerink and L. Joachim and S. Ghimire and
                      E. Vonbrunn and M. Büttner-Herold and M. Remke$^*$ and K.
                      Steiger$^*$ and R. Öllinger and R. Rad$^*$ and D. Wolff and
                      M. Feuerer and P. Hoffmann and M. Edinger and M. Rehli and
                      M. Tschurtschenthaler$^*$ and O. Kepp and G. Kroemer and E.
                      Thiele Orberg and S. E. Combs$^*$ and W. Herr and F.
                      Bassermann$^*$ and D. H. Busch and E. Holler and S.
                      Heidegger and H. Poeck},
      title        = {{T}issue-adapted {T}regs harness inflammatory signals to
                      promote intestinal repair from therapy-related injury.},
      journal      = {Signal transduction and targeted therapy},
      volume       = {10},
      number       = {1},
      issn         = {2095-9907},
      address      = {London},
      publisher    = {Macmillan Publishers, part of Springer Nature},
      reportid     = {DKFZ-2025-02622},
      pages        = {384},
      year         = {2025},
      abstract     = {Intestinal stem cells (ISCs) promote tissue repair after
                      genotoxic or immune-mediated injury. However, ISCs are
                      particularly sensitive to various stressors and primary
                      targets of overwhelming immune responses, such as interferon
                      γ (IFNγ)-mediated killing. In mouse models of radiation
                      therapy-induced gut damage and in biopsies from patients who
                      underwent allogeneic hematopoietic stem cell
                      transplantation, we observed IFNγ expression by intestinal
                      Treg cells. Treg cells leverage combined IFNγ and
                      interleukin 10 (IL-10) stimulation of ISCs to nurture the
                      growth of intestinal organoids through the activation of the
                      mTORC1 and Myc pathways. Similarly, Treg cells or the
                      combined addition of recombinant IFNγ and IL-10 promoted
                      the regeneration of organoids after irradiation, and both
                      cytokines were essential for ensuring epithelial
                      regeneration following acute intestinal tissue injury in
                      vivo. The exposure of organoids to growth factor-free
                      culture conditions revealed distinct EGF-like properties of
                      IFNγ and Wnt-like properties of IL-10. While IFNγ rapidly
                      induced epithelial proliferation, it depleted the pool of
                      ISCs in vitro. Only the combination of IFNγ and IL-10 led
                      to epithelial proliferation and organoid growth while
                      simultaneously ensuring ISC maintenance over time. Our
                      results reveal a context-dependent role of inflammatory
                      signaling in ISCs, through which Treg cells promote
                      epithelial repair following therapy-induced injury.},
      keywords     = {Animals / T-Lymphocytes, Regulatory: immunology /
                      T-Lymphocytes, Regulatory: pathology / Mice / Humans /
                      Interferon-gamma: genetics / Interferon-gamma: immunology /
                      Interleukin-10: genetics / Interleukin-10: immunology /
                      Intestines: immunology / Intestines: pathology / Intestines:
                      radiation effects / Intestines: injuries / Organoids:
                      immunology / Inflammation: immunology / Inflammation:
                      pathology / Inflammation: genetics / Intestinal Mucosa:
                      immunology / Intestinal Mucosa: pathology / Hematopoietic
                      Stem Cell Transplantation / Stem Cells: immunology / Stem
                      Cells: pathology / Interferon-gamma (NLM Chemicals) /
                      Interleukin-10 (NLM Chemicals) / IL10 protein, human (NLM
                      Chemicals)},
      cin          = {MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41290566},
      doi          = {10.1038/s41392-025-02476-5},
      url          = {https://inrepo02.dkfz.de/record/306581},
}