β-Glucan alleviates colitis by remodeling the colonic microenvironment and promoting interleukin-33-driven active eosinophil differentiation.

Abstract

Eosinophils play an essential role in intestinal homeostasis, yet the mechanisms governing their functions in intestine remain poorly defined. β-Glucan, an immunomodulator, has been shown to alleviate colitis, but whether it acts through eosinophils and the underlying mechanisms remains unclear. Here we show that β-Glucan pretreatment significantly attenuated dextran sulfate sodium (DSS)‑induced colitis in wild-type mice but not in eosinophil-deficient mice, indicating an eosinophil-dependent protective effect. β‑Glucan increased the frequency and absolute number of colonic active eosinophils (A-Eos), which correlated with reduced disease severity. Mechanistically, β‑glucan upregulated interleukin-33 (IL‑33) expression in colon tissues. Colon conditioned medium (CM) from β‑glucan‑treated mice directly promoted the differentiation of bone marrow‑derived eosinophils (BM-Eos) into CD80⁺PD‑L1⁺ A‑Eos ex vivo, and this effect was completely reversed by IL-33 neutralization. Our findings identify a novel β-glucan-IL-33-A-Eos axis and provide a mechanistic basis for using β-glucan as an immunomodulatory strategy to prevent inflammatory bowel disease (IBD).