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The interleukin 22–oncostatin M axis promotes intestinal inflammation and tumorigenesis

GSE269578 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/03/27 Platform GPL20301
Summary
Multicellular cytokine networks orchestrate the onset and progression of intestinal inflammation and colitis-associated cancer (CAC). Interleukin 22 (IL-22), a member of the IL-10 superfamily, is known for promoting epithelial cell recovery but can inadvertently fuel inflammation and tumorigenesis. Here, we demonstrate that IL-22, derived from group 3 innate lymphoid cells (ILC3), triggers oncostatin M (OSM) responsiveness in intestinal epithelial cells by activating STAT3 and upregulating OSM receptor (OSMR) expression. OSM, a member of the IL-6 cytokine family implicated in inflammatory bowel disease, collaborates with IL-22 to sustain STAT3 activation, promoting proinflammatory adaptations and immune cell chemotaxis to the intestine. Conditional deletion of OSMR in epithelial cells protects mice from colitis and CAC. Additionally, pharmacological blockade of OSM reduces the progression of established CAC. Our study reveals a novel mechanism by which OSM sustains intestinal inflammation and CAC, identifying the IL-22-OSM axis as a promising therapeutic target.
Published in
The IL-22-oncostatin M axis promotes intestinal inflammation and tumorigenesis
Cineus R, Luo Y, Saliutina M et al. · Nature immunology 2025 · PMID 40447860 · doi:10.1038/s41590-025-02149-z
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Also filed as BioProject PRJNA1122565 and SRA study SRP513214. Searching any of these in the dataset finder brings you back here.

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