Fischer, Julius C. and Gottert, Sascha and Giller, Maximilian and Heinrich, Paul and Fan, Kaiji and Khalid, Omer and Walther, Caroline N. and Drießlein, Maria and Nefzger, Sophie M. and Eisenkolb, Gabriel and Timnik, Vincent R. and Jarosch, Sebastian and Klostermeier, Lena and Engleitner, Thomas and Strieder, Nicholas and Gebhard, Claudia and Diederich, Sarah and Schmid, Nicole A. and Lansink Rotgerink, Laura and Joachim, Laura and Ghimire, Sakhila and Vonbrunn, Eva and Buttner-Herold, Maike and Remke, Marianne and Steiger, Katja and Ollinger, Rupert and Rad, Roland and Wolff, Daniel and Feuerer, Markus and Hoffmann, Petra and Edinger, Matthias and Rehli, Michael and Tschurtschenthaler, Markus and Kepp, Oliver and Kroemer, Guido and Thiele Orberg, Erik and Combs, Stephanie E. and Herr, Wolfgang and Bassermann, Florian and Busch, Dirk H. and Holler, Ernst and Heidegger, Simon and Poeck, Hendrik (2025) Tissue-adapted Tregs harness inflammatory signals to promote intestinal repair from therapy-related injury. SIGNAL TRANSDUCTION AND TARGETED THERAPY, 10 (1): 384. ISSN 2095-9907, 2059-3635
Full text not available from this repository. (Request a copy)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 gamma (IFN gamma)-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 IFN gamma expression by intestinal Treg cells. Treg cells leverage combined IFN gamma 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 IFN gamma 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 IFN gamma and Wnt-like properties of IL-10. While IFN gamma rapidly induced epithelial proliferation, it depleted the pool of ISCs in vitro. Only the combination of IFN gamma 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; REGULATORY T-CELLS; BONE-MARROW-TRANSPLANTATION; INTERFERON-GAMMA; IFN-GAMMA; STEM-CELLS; INTERLEUKIN-10; MICE; INHIBITION; INDUCTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Jun 2026 11:28 |
| Last Modified: | 03 Jun 2026 11:28 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67360 |
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