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. In this study, we aim to assess the impact of OSM signaling in different resident cell types in the colon within the context of intestinal inflammation. To explore the transcriptional changes in colitis among various tissue-resident cells, we utilized single-cell sequencing to analyze the expression of OSM and OSMR in epithelial, stromal, and endothelial cells. We compared cells isolated from both steady-state and colitic mice. Colitis was induced by gavage of Helicobacter hepaticus and anti-IL-10R administration.