Interferon b drives intestinal regeneration after radiation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34613772.
- Also identified by DOI 10.1126/sciadv.abi5253 and PMC identifier 8494436.
- Licence recorded as CC BY-NC.
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Abstract
The cGAS-STING cytosolic DNA sensing pathway is critical for host defense. Here, we report that cGAS-STING–dependent type 1 interferon (IFN) response drives intestinal regeneration and animal recovery from radiation injury. <i>STING</i> 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. <i>cGAS</i> KO, <i>IFNAR1</i> KO, or <i>CCR2</i> KO also abrogates radiation-induced acute crypt inflammation and regeneration. Impaired intestinal regeneration and survival in <i>STING-</i>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<sup>+</sup> 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.