The interleukin 22–oncostatin M axis promotes intestinal inflammation and tumorigenesis [Epithelial_cells_BulkRNA-seq]

Multicellular cytokine networks regulate the onset of intestinal inflammation and colitis-associated cancer (CAC). Interleukin 22 (IL-22) promotes epithelial cell recovery but can also drive inflammation and tumorigenesis. We demonstrate that IL-22 from innate lymphoid cells activates STAT3 and increases OSM receptor expression in intestinal epithelial cells. This activation leads to sustained STAT3 activity via OSM, promoting inflammation and tumorigenesis. Deleting the OSM receptor or blocking OSM pharmacologically mitigates colitis and CAC. Our findings highlight the IL-22-OSM axis as a potential therapeutic target for these conditions. Overall design: Col1a2creERT2 and VillincreERT2 Osmr^fl/fl mice were treated with 75 mg/kg body weight of tamoxifen intraperitoneally daily for one week, following the Jackson Laboratory protocol. Control mice, either cre+ Osmr^fl/wt or Osmr^fl/fl without creERT2, also received tamoxifen. Colitis was induced by orally inoculating the mice with 1 × 10^8 CFU of H. hepaticus for two days, followed by weekly 1 mg injections of anti-IL10R antibody.