Th17 cells require the DNA repair sensor xeroderma pigmentosum complementation Group C to control oxidative DNA damage in a murine model

Abstract

T helper 17 cells play essential roles in mucosal immunity and autoimmunity, yet the mechanisms that protect these cells from oxidative DNA damage remainpoorly defined. Here we show, in a murine model, that the nucleotide excisionrepair sensor Xeroderma Pigmentosum Complementation Group C preservesgenomic stability and metabolic fitness during T helper 17 cell differentiation.Loss of this factor reduces interleukin 17 production and increases mitochon-drial reactive oxygen species and oxidative DNA damage, resulting in alteredmetabolic programs. Mechanistically, Xeroderma Pigmentosum Com-plementation Group C interacts with the base excision repair enzyme 8-oxoguanine DNA glycosylase, and its absence enhances oxidative lesion inci-sion activity, indicating defective coordination between DNA repair pathways. Restoring antioxidant capacity rescues cytokine production and limits DNA damage in deficient cells. Together, these findings identify Xeroderma Pig-mentosum Complementation Group C as a key coordinator of DNA repair and redox control required for T helper 17 cell function in inflammatory settings.