间充质干细胞通过调节性B细胞治疗肝移植术后免疫介导胆道炎症损伤的细胞与分子机制研究

免疫介导胆道炎症损伤所致的难治性胆道并发症是目前影响肝移植患者中长期生存的的最主要原因。研究证实除细胞免疫外，体液免疫也发挥重要作用。课题组的两项临床研究证实:具有多免疫靶点调节作用的间充质干细胞（MSC）可有效治疗骨髓移植后移植物抗宿主病和肝移植术后缺血性胆管炎（NTC02223897，Cell Mol Immunol，2015；Cytotherapy，2016），有效的受者T细胞亚群变化不显著，而调节性B细胞（Breg）比例明显上升（Stem Cells Transl Med，2014；Leukemia，2015)，提示MSC影响B细胞外周分化，特别是Breg发挥免疫调节作用，但MSC如何调节B细胞分化从而改善胆道损伤的机制并不清楚。本课题利用肝移植胆管炎模型和临床研究，通过体内体外实验明确MSC通过Breg治疗肝移植术后胆道炎症损伤的机制，为MSC治疗难治性胆道并发症提供理论依据。

Nowadays, immune-mediated cholangitis is considered as refractory bile complication, which is one of the main course affecting long-term survival after liver transplantation. Recently, many studies have showed that in addition to cellular immunity, humoral immunity also played an important role in immune-mediated cholangitis.In previous clinical study, we proved that MSC played a therapeutic role in GVHD after bone marrow transplantation (81570161) and ischemia type biliary lesions after liver transplantation (NTC02223897) (Cell Mol Immunol，2015；Cytotherapy；2016). Furthermore, we showed that with the effects of MSC（Stem Cells Transl Med，2014，2014，Leukemia，2015), the ratio of Breg cells increased significantly, while T cells was unchanged in the patients with effective therapy. Above all, MSC maybe play an immunomodulatory effects in affecting the differentiation of B cells, especially Breg cells. However, the exact mechanisms are still unclear. Therefore, this study intends to explore the mechanisms of MSC in promoting immune-mediated cholangitis using a rat model of cholangitis after liver transplantation. In this setting, we aim to provide new mechanisms for immune-mediated cholangitis and a new theoretical basis for MSC in enhancing immune-mediated cholangitis after liver transplantation.