| 著者 |
Trsan T, Peng V, Krishna C, Ohara TE, Beatty WL, Sudan R, Kanai M, Krishnamoorthy P, Rodrigues PF, Fachi JL, Grajales-Reyes G, Jaeger N, Fitzpatrick JAJ, Cella M, Gilfillan S, Nakata T, Jaiswal A, Stappenbeck TS, Daly MJ, Xavier RJ, Colonna M.
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| Abstract |
Recent advances in human genetics have shed light on the genetic factors contributing to inflammatory diseases, particularly Crohn's disease (CD), a prominent form of inflammatory bowel disease. Certain risk genes associated with CD directly influence cytokine biology and cell-specific communication networks. Current CD therapies primarily rely on anti-inflammatory drugs, which are inconsistently effective and lack strategies for promoting epithelial restoration and mucosal balance. To understand CD's underlying mechanisms, we investigated the link between CD and the FGFR1OP gene, which encodes a centrosome protein. FGFR1OP deletion in mouse intestinal epithelial cells disrupted crypt architecture, resulting in crypt loss, inflammation, and fatality. FGFR1OP insufficiency hindered epithelial resilience during colitis. FGFR1OP was crucial for preserving non-muscle myosin II activity, ensuring the integrity of the actomyosin cytoskeleton and crypt cell adhesion. This role of FGFR1OP suggests that its deficiency in genetically predisposed individuals may reduce epithelial renewal capacity, heightening susceptibility to inflammation and disease.
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