肠上皮细胞及其分泌形成的黏液层组成的肠黏膜屏障在维持肠道稳态中发挥至关重要的作用。肠上皮细胞稳态失衡或功能缺陷导致异常的炎症免疫反应是炎症性肠病（inflammatory bowel disease, IBD）发生、发展的关键环节。我们以往研究发现全基组敲除分选连接蛋白10（SNX10）可减轻DSS诱导的小鼠肠道炎症及黏膜损伤；近期研究发现干扰结肠上皮细胞SNX10表达能明显减轻DSS诱导的结肠炎症，上调分子伴侣介导的自噬（CMA），提示SNX10有可能成为IBD治疗的新靶点。本项目将在此基础上利用肠上皮细胞SNX10条件敲除鼠DSS诱导的急性IBD模型，以及肠上皮细胞SNX10敲低IL-10-/-小鼠慢性IBD模型，进一步研究靶向干预肠上皮细胞SNX10对小鼠IBD发生、发展的影响，并从CMA角度探讨其分子机制，有可能为IBD提供新的治疗途径和药物筛选靶标。

Intestinal epithelial cells and their associated mucus layer serve as a physical barrier against the external environment and play a vital role in maintaining intestinal homeostasis. Loss of homeostasis or dysfunction of intestinal epithelial cells resulting in aberrant inflammatory immune response is considered as the critical process for the occurrence and development of inflammatory bowel disease (IBD). Our previous studies have found that global gene knock-out sorting nexin 10 (SNX10) alleviated intestinal inflammation and mucosa damage in DSS induced mice IBD. Recently, we found that interference of SNX10 expression in colonic epithelial cells can also significantly improve the colonic inflammation induced by DSS, and up-regulate chaperone-mediated autophagy, suggesting SNX10 might be a potential therapeutic target for IBD. In this project, we will take the advantage of intestinal epithelium SNX10 conditional knockout mouse IBD induced by DSS, and intestinal epithelium SNX10 knock-down IL-10-/- mouse IBD to further explore the impact of targeted intervention of intestinal epithelial SNX10 on the development of IBD and underlying molecular mechanisms related to CMA. Our findings may contribute a new therapeutic target for drug screening of IBD.