Resistin-like molecule α enhances myeloid cell activation and promotes colitis

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Resistin-like molecule (Relm) α is a secreted protein and a hallmark signature gene for alternatively activated macrophages. Relm-α is highly induced by allergic inflammatory triggers and perceived to promote tissue repair. Yet the function of Relm-α remains unknown.


We sough to determine the role of Relm-α in dextran sodium sulfate (DSS)-induced colonic injury.


The cellular source of Relm-α was determined after oral DSS-induced colitis.Retnla−/−mice were generated, subjected to DSS treatment, and monitored for disease progression (clinical and histopathologic features). Cytokine production in the supernatants ofex vivocolon cultures, and of LPS-stimulated macrophages incubated with Relm-α was assessed. Relm-α was administered intraperitoneally, and the cellular recruitment to the peritoneum was assessed.


After innate intestinal stimulation with DSS, Relm-α was highly expressed by eosinophils and epithelial cells.Retnlagene-targeted mice were protected from DSS-induced colitis (eg, decreased diarrhea, rectal bleeding, colon shortening, disease score, and histopathologic changes). Relm-α coactivated IL-6 and TNF-α release and inhibited IL-10 release from LPS-activated bone marrow-derived macrophages. Consistent with these finding, colon cultures of DSS-treatedRetnla−/−mice produced decreased IL-6 and increased IL-10ex vivo. Furthermore,Retnla−/−mice had substantially decreased c-Jun N-terminal kinase phosphorylationin vivo.In vivoadministration of Relm-α initiated cellular recruitment to the peritoneum, and Relm-α was able to induce eosinophil chemotaxisin vitro.


These findings demonstrate a central proinflammatory role for Relm-α in colonic innate immune responses, identifying a novel pathway for regulation of macrophage activation.

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