Manzanillo Paolo, Mouchess Maria, Ota Naruhisa, Dai Bingbing, Ichikawa Ryan, Wuster Arthur, Haley Benjamin, Alvarado Gabriela, Kwon Youngsu, Caothien Roger, Roose-Girma Meron, Warming Soren, McKenzie Brent S, Keir Mary E, Scherl Alexis, Ouyang Wenjun, Yi Tangsheng
Department of Immunology Discovery, Genentech Inc., South San Francisco, CA 94080;
Department of Immunology Discovery, Genentech Inc., South San Francisco, CA 94080.
Immunohorizons. 2018 May 30;2(5):164-171. doi: 10.4049/immunohorizons.1800027.
Intestinal epithelial cells form a physical barrier that is tightly regulated to control intestinal permeability. Proinflammatory cytokines, such as TNF-α, increase epithelial permeability through disruption of epithelial junctions. The regulation of the epithelial barrier in inflammatory gastrointestinal disease remains to be fully characterized. In this article, we show that the human inflammatory bowel disease genetic susceptibility gene plays a key role in regulating gut epithelial permeability. C1ORF106 directly interacts with cytohesins to maintain functional epithelial cell junctions. -deficient mice are hypersensitive to TNF-α-induced increase in epithelial permeability, and this is associated with increased diarrhea. This study identifies C1ORF106 as an epithelial cell junction protein, and the loss of C1ORF106 augments TNF-α-induced intestinal epithelial leakage and diarrhea that may play a critical role in the development of inflammatory bowel disease.
肠上皮细胞形成一个受到严格调控以控制肠道通透性的物理屏障。促炎细胞因子，如肿瘤坏死因子-α（TNF-α），通过破坏上皮连接来增加上皮通透性。炎症性胃肠疾病中上皮屏障的调节仍有待充分阐明。在本文中，我们表明人类炎症性肠病遗传易感性基因在调节肠道上皮通透性中起关键作用。C1ORF106直接与细胞衔接蛋白相互作用以维持功能性上皮细胞连接。C1ORF106缺陷小鼠对TNF-α诱导的上皮通透性增加高度敏感，这与腹泻增加有关。本研究将C1ORF106鉴定为一种上皮细胞连接蛋白，C1ORF106的缺失会加剧TNF-α诱导的肠道上皮渗漏和腹泻，这可能在炎症性肠病的发展中起关键作用。
