| First Author | Leibowitz BJ | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 41 | Pages | eabi5253 |
| PubMed ID | 34613772 | Mgi Jnum | J:313161 |
| Mgi Id | MGI:6791279 | Doi | 10.1126/sciadv.abi5253 |
| Citation | Leibowitz BJ, et al. (2021) Interferon b drives intestinal regeneration after radiation. Sci Adv 7(41):eabi5253 |
| abstractText | The cGAS-STING cytosolic DNA sensing pathway is critical for host defense. Here, we report that cGAS-STINGâdependent 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-β 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-β treatment given 48 hours after irradiation but not by wild-type (WT) bone marrow. IFN-β 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-β production in the niche couples ISC injury and regeneration and its potential use to treat acute radiation injury. |
