Alleviation of colonic inflammation by Lypd8 in a mouse model of inflammatory bowel disease
Alleviation of colonic inflammation by Lypd8 in a mouse model of inflammatory bowel disease
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DOI：
10.1093/intimm/dxab012
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发表时间：
2021-04-05
影响因子：
4.4
通讯作者：
Takeda, Kiyoshi
中科院分区：
文献类型：
--
作者：
Hsu, Chiao-Ching;Okumura, Ryu;Takeda, Kiyoshi
肠粘膜屏障功能障碍导致炎症性肠病（IBD）。事实上，IBD患者肠道中的粘膜屏障损伤是由屏障分子的表达降低引起的。含有Ly 6/Plaur结构域8（Lypd 8）的蛋白质将微生物群与结肠上皮层分离。在这项研究中，我们发现Lypd 8（-/-）小鼠，其中鞭毛细菌侵入结肠粘膜表面，当由高脂饮食（HFD）诱导生态失调时，发生自发性结肠炎。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性的人LYPD 8（hLYPD 8）蛋白是否有效。用hLYPD 8蛋白的口服和肛门治疗改善Lypd 8（-/-）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hLYPD 8蛋白补充剂对IBD的治疗潜力。
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.