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Alleviation of colonic inflammation by Lypd8 in a mouse model of inflammatory bowel disease
International Immunology ( IF 4.8 ) Pub Date : 2021-04-05 , DOI: 10.1093/intimm/dxab012
Chiao-Ching Hsu 1, 2 , Ryu Okumura 1, 2 , Daisuke Motooka 3, 4 , Reo Sasaki 1 , Shota Nakamura 3, 4 , Tetsuya Iida 3, 5 , Kiyoshi Takeda 1, 2, 4
Affiliation  

Abstract
Dysfunction of the intestinal mucosal barrier causes inflammatory bowel diseases (IBDs). Indeed, mucosal barrier impairment in the gut of IBD patients results from decreased expression of barrier molecules. Ly6/Plaur domain containing 8 (Lypd8) segregates microbiota from the colonic epithelial layer. In this study, we found that Lypd8/− mice, in which flagellated bacteria invaded the mucosal surface of the colon, developed spontaneous colitis when dysbiosis was induced by a high-fat diet (HFD). On the basis of this finding, we assessed whether the application of human LYPD8 (hLYPD8) protein exhibiting the glycan-dependent inhibition of bacterial motility is effective in a colitis model. Oral and anal treatments with hLYPD8 protein ameliorate dextran sulfate sodium-induced colitis and HFD-induced colitis in Lypd8/− mice. These results indicate a therapeutic potential of hLYPD8 protein supplementation for IBD.


中文翻译:

Lypd8 减轻炎症性肠病小鼠模型中的结肠炎症

摘要
肠黏膜屏障功能障碍会导致炎症性肠病 (IBD)。事实上,IBD 患者肠道中的黏膜屏障受损是由于屏障分子表达减少所致。含有 8 个 (Lypd8) 的 Ly6/Plaur 结构域将微生物群与结肠上皮层分离。在这项研究中,我们发现Lypd8 - /-当高脂肪饮食 (HFD) 诱导生态失调时,小鼠体内的鞭毛细菌侵入结肠黏膜表面,从而发展为自发性结肠炎。基于这一发现,我们评估了在结肠炎模型中应用表现出聚糖依赖性抑制细菌运动的人 LYPD8 (hLYPD8) 蛋白是否有效。用 hLYPD8 蛋白进行口服和肛门治疗可改善Lypd8 - /-小鼠中葡聚糖硫酸钠诱导的结肠炎和 HFD 诱导的结肠炎。这些结果表明 hLYPD8 蛋白补充剂对 IBD 的治疗潜力。
更新日期:2021-04-05
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