| First Author | Yang W | Year | 2022 |
| Journal | Adv Sci (Weinh) | Volume | 9 |
| Issue | 10 | Pages | e2103035 |
| PubMed ID | 35119210 | Mgi Jnum | J:350613 |
| Mgi Id | MGI:7664291 | Doi | 10.1002/advs.202103035 |
| Citation | Yang W, et al. (2022) IL-36gamma and IL-36Ra Reciprocally Regulate Colon Inflammation and Tumorigenesis by Modulating the Cell-Matrix Adhesion Network and Wnt Signaling. Adv Sci (Weinh) 9(10):e2103035 |
| abstractText | Inflammatory bowel disease and colorectal cancer are associated with dysregulation of cytokine networks. However, it is challenging to target cytokines for effective intervention because of the overlapping functions and unpredictable interactions of cytokines in such diverse networks. Here, it is shown that IL-36gamma and IL-36Ra, an agonist and an antagonist for IL-36R signaling respectively, reciprocally regulate the experimental colitis and the colon cancer development in mice. Knockout or neutralization of IL-36gamma alleviates dextran sulfate sodium (DSS)-induced colitis and inhibits colon cancer development, whereas knockout of IL-36Ra exacerbates DSS-induced colitis and promotes colonic tumorigenesis in multiple colon cancer models in mice. Mechanistically, IL-36gamma upregulates extracellular matrix and cell-matrix adhesion molecules and facilitates Wnt signaling, which is mitigated by IL-36Ra or IL-36gamma neutralizing antibody. Consistently, IL-36gamma levels are positively correlated with extracellular matrix levels and beta-catenin levels in human colorectal tumor biopsies. These findings suggest the critical role of IL-36gamma and IL-36Ra in gut inflammation and tumorigenesis and indicate that targeting the IL-36gamma/IL-36Ra signal balance provides potential therapeutic strategy for inflammatory bowel disease and gastrointestinal cancers. |
