RADX protects against intestinal inflammation by restraining IFI16-mediated innate immunity

ABSTRACT: Genomic instability is increased in patients with inflammatory bowel disease (IBD), yet whether it contributes directly to disease pathogenesis remains unclear. Here, we identify RADX, a structural antagonist to RAD51 and a key regulator of replication fork stability, as a critical suppressor of intestinal inflammation by limiting innate immune sensing of replication-associated DNA damage. RADX deficiency exacerbates experimental colitis, with macrophages serving as the principal mediators of this phenotype. Mechanistically, RADX competes with the DNA sensor IFI16 for binding to single-stranded DNA (ssDNA). Loss of RADX promotes ssDNA accumulation, triggering IFI16-dependent activation of NF-kB signaling and inflammasome assembly, thereby driving intestinal inflammation. Consistent with th

SUBMITTER: Yuxia Zhang 

PROVIDER: S-SCDT-10_1038-S44321-026-00494-6 | biostudies-other |

REPOSITORIES: biostudies-other