| First Author | Hao J | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 2820 |
| PubMed ID | 38561332 | Mgi Jnum | J:348971 |
| Mgi Id | MGI:7619381 | Doi | 10.1038/s41467-024-45616-1 |
| Citation | Hao J, et al. (2024) Dysregulation of Wnt/beta-catenin signaling contributes to intestinal inflammation through regulation of group 3 innate lymphoid cells. Nat Commun 15(1):2820 |
| abstractText | RORgammat(+) group 3 innate lymphoid cells (ILC3s) are essential for intestinal homeostasis. Dysregulation of ILC3s has been found in the gut of patients with inflammatory bowel disease and colorectal cancer, yet the specific mechanisms still require more investigation. Here we observe increased beta-catenin in intestinal ILC3s from inflammatory bowel disease and colon cancer patients compared with healthy donors. In contrast to promoting RORgammat expression in T cells, activation of Wnt/beta-catenin signaling in ILC3s suppresses RORgammat expression, inhibits its proliferation and function, and leads to a deficiency of ILC3s and subsequent intestinal inflammation in mice. Activated beta-catenin and its interacting transcription factor, TCF-1, cannot directly suppress RORgammat expression, but rather alters global chromatin accessibility and inhibits JunB expression, which is essential for RORgammat expression in ILC3s. Together, our findings suggest that dysregulated Wnt/beta-catenin signaling impairs intestinal ILC3s through TCF-1/JunB/RORgammat regulation, further disrupting intestinal homeostasis, and promoting inflammation and cancer. |
