EphB2/ephrin-B1通路介导BMSC-EVs在溃疡性结肠炎中的免疫调节机制及复方苦参汤协同作用研究

肠黏膜固有层CD4+T淋巴细胞亚群异常分化是导致UC发病关键因素。研究表明,Eph家族蛋白异常表达与UC发病有关,Eph/ephrin通路在UC发生中起重要作用,BMSCs可通过EphB2/ephrin-B1通路调节UC的T细胞增殖和分化。高表达EphB2的BMSCs具有较强肠道迁移能力,EVs携带EphB2进行远距离细胞间通讯。前期发现,BMSC-EVs可经旁分泌方式到达UC受损肠黏膜发挥免疫调节作用,复方苦参汤对UC有较好疗效。因此,推断构建过表达EphB2的BMSC-EVs,可增强其迁移至UC受损肠黏膜的能力,通过EphB2/ephrin-B1通路调节T细胞的免疫功能。本课题组拟采用分子生物学、慢病毒感染等方法,研究复方苦参汤协同过表达EphB2的BMSC-EVs迁移到UC受损肠黏膜,通过EphB2/ephrin-B1通路放大其对UC的免疫作用,为开拓该病的临床治疗提供新的治疗策略。

Abnormal differentiation of CD4+T lymphocyte subsets in the lamina propria of intestinal mucosa is a key factor to the development of ulcerative colitis (UC). Studies prove that the abnormal expression of Eph family protein is associated with the onset of UC, and Eph/ephrin pathway plays an important role in the pathogenesis of UC. Bone mesenchymal stem cells (BMSCs) can regulate T cells proliferation and differentiation in UC by EphB2/ephrin-B1 pathway. A subpopulation of BMSCs expressing high levels of EphB2 has enhanced ability to engraft to the resident intestinal cellular pool. Novel findings have revealed that EphB2 can also be incorporated into exosomes (extracellular vesicles, EVs) and cause long-distance intercellular communication independently of direct cell-cell contact. The preliminary study has found that BMSC-EVs are able to travel to damaged intestinal tissue in UC by paracrine way and inhibit the inflammatory response. Compound Sophorae Decoction has a preferable therapeutic effect on UC. On the basis of above findings, we suggest that BMSC-EVs, which are over-expressed EphB2, can increase their migratory capacity to intestinal mucosa areas, and regulate the immune function of T cells through EphB2/ephrin-B1 pathway. Therefore, this research aims at using molecular biology and lentivirus infection method, to explore whether BMSC-EVs overexpressed EphB2 can enhance the ability to migrate to damaged intestinal tissue in UC, and how to amplify its immune function through EphB2/ephrin-B1 pathway to improve the healing process. This will provide a new treatment strategy for clinical treatment of UC.