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| Item Type: | Article |
|---|---|
| Title: | The IL-22–oncostatin M axis promotes intestinal inflammation and tumorigenesis |
| Creators Name: | Cineus, R., Luo, Y., Saliutina, M., Manna, S., Cancino, C.A., Velasco Blázquez, L., Wang, L., Bösel, D., Abdelrahman, A., Klementowicz, J.E., Scherl, A., Hainbuch, S., Bréart, B., Kwon, G., Konopka, A., Guerra, G.M., von Coburg, E., Gerbeth, Lo., Roels, J., Heinrich, F., Müller, N., Durek, P., Deigendesch, N., Ziai, J., Hung, J., Conrad, T., Kühl, A.A., Wirtz, S., Löhning, M., Keir, M., Diefenbach, A., Mashreghi, M.F., Siegmund, B., Schumann, M., Romagnani, C., West, N.R. and Hegazy, A.N. |
| Abstract: | Multicellular cytokine networks drive intestinal inflammation and colitis-associated cancer (CAC). Interleukin-22 (IL-22) exerts both protective and pathogenic effects in the intestine, but the mechanisms that regulate this balance remain unclear. Here, we identify that IL-22 directly induces responsiveness to the IL-6 family cytokine oncostatin M (OSM) in intestinal epithelial cells (IECs) by activating STAT3 and upregulating the OSM receptor. In turn, OSM synergizes with IL-22 to sustain STAT3 activation in IECs and promote proinflammatory epithelial adaptation and immune cell chemotaxis to the inflamed intestine. Conditional deletion of the OSM receptor in IECs protects mice from both colitis and CAC, and pharmacological blockade of OSM attenuates established CAC. Thus, IL-22 and OSM form a pathogenic circuit that drives inflammation and tumorigenesis. Our findings reveal a previously unknown mechanism by which OSM supports intestinal pathology and highlight the IL-22–OSM axis as a promising therapeutic target for inflammatory bowel disease and CAC. |
| Keywords: | Carcinogenesis, Colitis, Colitis-Associated Neoplasms, Epithelial Cells, Inbred C57BL Mice, Inflammation, Interleukin-22, Interleukins, Intestinal Mucosa, Knockout Mice, Oncostatin M, Oncostatin M Receptors, STAT3 Transcription Factor, Signal Transduction, Animals, Mice |
| Source: | Nature Immunology |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Volume: | 26 |
| Number: | 6 |
| Page Range: | 837-853 |
| Date: | June 2025 |
| Additional Information: | Leif S.-H. Ludwig and Ashley Sanders are members of the TRR241 IBDome Consortium. |
| Official Publication: | https://doi.org/10.1038/s41590-025-02149-z |
| PubMed: | View item in PubMed |
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