人胚胎来源MSC通过下调结肠上皮MHC-II表达对IBD的治疗及免疫调节机制研究

炎症性肠病（IBD）是一类免疫介导的肠道非特异性炎症，传统药物治疗效果不佳且副作用较大。间充质干细胞（MSC）具有良好的免疫调节能力，有望成为治疗IBD的新方法。本研究采用人胚胎干细胞来源MSC（T-MSC），前期已建立T-MSC静脉注射治疗小鼠DSS结肠炎模型，结肠组织转录组测序提示治疗组MHC-II相关基因表达下调，进一步检测结肠原代细胞发现治疗组上皮细胞MHC-II表达减少。MHC-II与抗原提呈、免疫应答等密切相关，其表达及功能可调控辅助T淋巴细胞（Th细胞）亚群及细胞因子分泌，改变免疫应答状态。据此推测T-MSC可能通过下调结肠上皮MHC-II表达，改变Th细胞亚群，缓解小鼠肠道炎症。本研究拟通过检测治疗模型中结肠上皮MHC-II表达及功能、固有层Th细胞亚群、体外共培养等方面进行研究，阐释T-MSC通过下调MHC-II实现免疫调节的关键分子机制，为其后续投入临床提供理论依据。

Inflammatory bowel disease (IBD) is characterized by nonspecific inflammation of the gut due to abnormal immune response. Traditional drug therapy is of limit effect and accompanies with various side-effects. Mesenchymal stem cell (MSC) is becoming a promising alternative in the treatment of IBD due to its strong immunomodulatory function. Here we developed human embryonic stem cell derived MSC (so called T-MSC) and found intravenous T-MSC injection was effective in the treatment of mouse DSS colitis. Further RNA-sequencing of colon samples indicated MHC-II related genes were down-regulated in treatment group. Both colon epithelial cells and lamina propria cells were analyzed by flow cytometry and we found T-MSC group exhibited a decrease in MHC-II expression in epithelial cells. MHC-II molecules are involved in biological processes such as antigen presentation and immune response. They are capable to regulate the subtype distribution and cytokine secretion of T helper cells in both direct and indirect manners. Based on previous mentioned results, we speculate T-MSC might exert its therapeutic function by down regulating MHC-II expression in colon epithelial cells and thus influence the subtype and cytokine secretion of Th cells to alleviate DSS colitis. Several parts of experiments are required to prove the hypothesis, including the detection of epithelial MHC-II expression, Th cell subtype distribution in colon lamina propria lymphocytes. Further functional evaluation of MHC-II in colon epithelial cells and in vitro co-culture of MSC and epithelial cells are also required. The research aims to explore the immunomodulatory function of T-MSCs by down-regulating MHC-II molecules and this provide a new insight in the therapeutic potential of T-MSCs and prepares for their future clinical application in IBD treatment.