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Inflammatory immunity exacerbates tissue damage in the tissue injury. Resolution of the inflammation trigger tissue repair and regeneration. We report here that the extracellular PKM2 (EcPKM2) modulates immunity at colon damage site by facilitating M2 macrophage polarization in response to Dextran Sodium Sulfate (DSS)-induced damage. The effects of EcPKM2 on macrophage polarity led to decreased inflammation and facilitated the repairment of colon damages due to a reduction in epithelial cell death in a DSS-induced Ulcerative colitis mouse model. Interestingly, EcPKM2 facilitates intestinal mucosal lining repair by promoting colon epithelial proliferation. EcPKM2 protects intestinal epithelial cells from death and promotes the epithelial cell proliferation by promoting M2 macrophages’ polarity. Our study suggests a potential new therapeutic strategy by targeting macrophage polarity for Ulcerative Colitis treatment.
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Li et al. (2026) studied this question.
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