Intravenous immunoglobulin enhances intestinal stem cell regeneration to mitigate radiation-induced enteritis via promoting β-catenin nuclear translocation.

Radiation-induced enteritis (RIE), a common adverse effect after radiotherapy for pelvic, abdominal, and retroperitoneal tumors, has no effective treatment. Our previous study showed that intravenous immunoglobulin (IVIg) ameliorated radiation toxicity. Here, we investigated the role of IVIg in enhancing intestinal stem cell (ISC) regeneration to mitigate RIE and its underlying mechanism. In a mouse RIE model, IVIg improved tissue repair, reduced intestinal epithelial apoptosis and pyroptosis, decreased inflammatory factors, enhanced antioxidant capacity, and alleviated DNA damage. Notably, IVIg promoted the proliferation of OLFM4+ and LGR5+ ISCs in crypts and mitigated radiation-induced enteroid damage in vitro. Lineage tracing revealed that IVIg enhanced LGR5+ ISCs and their daughter cell survival. Mechanistically, IVIg promoted β-catenin nuclear translocation, and the β-catenin inhibitor MSAB diminished IVIg's radioprotective effects. Collectively, IVIg combats RIE by enhancing ISC regeneration via β-catenin nuclear translocation, highlighting its potential as an RIE therapeutic candidate.