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Eosinophil-specific deletion of COX-2 (Ptgs2\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    eoCre\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    ) reduced IL-22 production and exacerbated DSS- and trinitrobenzene sulfonic acid (TNBS)-induced colitis, characterized by greater weight loss, higher disease activity, colon shortening, and epithelial injury. Administration of recombinant IL-22 reversed these phenotypes. Mechanistically, eosinophil-derived COX-2 enhanced IL-22 production by type 3 Innate lymphoid cells (ILC3s) through prostaglandin E2 (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ) signaling. Consistently, Ptgs2\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    eoCre\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice exhibited reduced colonic PGE\n                    <jats:sub>2<\/jats:sub>\n                    levels, while PGE\n                    <jats:sub>2<\/jats:sub>\n                    analog treatment restored IL-22 production and mucosal protection. Our findings identify eosinophil-derived COX-2 and PGE\n                    <jats:sub>2<\/jats:sub>\n                    as a critical regulator of IL-22 production during colitis, uncovering a eosinophil\u2013ILC3 cross talk that safeguards the intestinal barrier and represents a promising therapeutic target in IBD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2525334123","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:10:45Z","timestamp":1777921845000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Eosinophil-derived COX-2 protects against experimental colitis through the PGE\n                    <sub>2<\/sub>\n                    \u2013IL-22 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