{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:15:57Z","timestamp":1785251757145,"version":"3.55.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract that frequently requires long-term immunosuppressive therapy, which increases the risk of infections and other complications. During active disease, intestinal bleeding is common and leads to the release of free luminal heme, a pro-inflammatory molecule that can disrupt mucosal integrity, fuel microbial dysbiosis, and amplify inflammation. Interleukin-22 (IL-22) plays a protective role in the gut by promoting epithelial barrier integrity and wound healing. More recently, IL-22 has been shown to induce hemopexin, a heme scavenger protein that limits heme availability and suppresses bacterial growth during systemic infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here we investigate the protective role of IL-22 and hemopexin in the context of colitis using the dextran sodium sulphate (DSS) acute colitis model in mice. Wild-type (Wt) and <jats:italic>Il22ra1<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice were used to evaluate the effects of exogenous hemopexin and hemin treatments on colitis severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IL-22 signaling was crucial for the induction of hemopexin in the colon, as <jats:italic>Il22ra1<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice exhibited limited hemopexin induction and more severe colitis, which could be reversed by recombinant hemopexin administration. Additionally, hemin treatment, known to upregulate heme oxygenase-1 (HO-1), failed to show full protective effects in <jats:italic>Il22ra1<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice, suggesting that IL-22 signaling contributes to the anti-inflammatory and antioxidant effects of hemin by inducing hemopexin and HO-1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings reveal a critical protective role for IL-22 by increasing the amount of hemopexin and HO-1 production in the colon, which could be part of a protective mechanism that mitigates DSS-induced colonic inflammation. Given its epithelial-specific and immunomodulatory activity, IL-22 represents a promising therapeutic approach for IBD. Furthermore, hemopexin itself may serve as an adjunct therapy during active disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1614466","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T04:10:19Z","timestamp":1753675819000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Hemopexin and HO-1 induction during acute colitis in mice is dependent on interleukin-22"],"prefix":"10.3389","volume":"16","author":[{"given":"Ayodeji 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