Interferon beta drives intestinal regeneration after radiation

Here, we report that cGAS-STING–dependent type 1 interferon (IFN) response drives intestinal regeneration and animal recovery from radiation injury. STING deficiency has no effect on radiation-induced DNA damage or crypt apoptosis but abrogates epithelial IFN beta production, local inflammation, innate transcriptional response, and subsequent crypt regeneration. cGAS KO, IFNAR1 KO, or CCR2 KO also abrogates radiation-induced acute crypt inflammation and regeneration.

Impaired intestinal regeneration and survival in STING-deficient mice are fully rescued by a single IFN beta treatment given 48 hours after irradiation but not by wild-type (WT) bone marrow. IFN treatment remarkably improves the survival of WT mice and Lgr5+ stem cell regeneration through elevated compensatory proliferation and more rapid DNA damage removal. Our findings support that inducible IFN production in the niche couples ISC injury and regeneration and its potential use to treat acute radiation injury.