Tissue-adapted Tregs harness inflammatory signals to promote intestinal repair from therapy-related injury.

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 T_reg cells. T_reg 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, T_reg cells or the combined addition of recombinant IFNγ and IL-10 promoted the regeneration of organoids after i

SUBMITTER: Fischer JC 

PROVIDER: S-EPMC12647259 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature