The interleukin 22–oncostatin M axis promotes intestinal inflammation and tumorigenesis [scRNA-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.