Tim-3/galectin-9信号通路介导肺移植术后急性排斥反应的作用及机制研究

Tim-3 expressed primarily on activated CD4+Th1, Th17 cell surface, and galectin-9 was proved to be the natural ligand for Tim-3. By binding of Tim-3 in the surface of immune cells and activation of Tim-3/galectin-9 signaling pathway, which played an important role in mediating immune tolerance in transplantation throgh inducing effector T cells apoptosis and reducing immune responses, but its role in acute allograft rejection atfer lung transplantation was unclear. In the preliminary study, by using rat and mouse orthotopic left lung transplantation model, we firstly showed that Tim-3/galectin-9 signaling pathway involved in acute rejection after lung transplantation process, and activation of the signaling pathway by recombinant galectin-9 could reduce acute rejection reactions. To explore the role of Tim-3/galectin-9 signaling pathway involved in the rejection after lung transplantation by means of further experiments, such as producing lung protection through regulating the Th1/Th17/Treg immune balance. This study can clarify the immunological mechanisms of Tim-3/galectin-9 signaling pathway regulating acute rejection after lung transplantation, and thus provide a new target for clinically treating acute rejection responses after lung transplantation.

Tim-3主要表达于活化的CD4+Th1、Th17细胞表面，galectin-9被证实是Tim-3的天然配体，与Tim-3结合后激活Tim-3/galectin-9信号通路，诱导效应T细胞产生抑制性免疫应答反应，在器官移植领域可介导移植物的免疫耐受，但其在肺移植中的作用尚不清楚。本研究前期结果发现：借助肺移植模型，首次发现Tim-3/galectin-9信号通路参与了肺移植术后急性排斥反应过程，应用重组galectin-9激活该信号通路可减轻急性排斥反应的发生。本研究将进一步探求Tim-3/galectin-9信号通路参与肺移植术后急性排斥反应的作用机制，通过介导Th1/Th17/Treg细胞间的免疫平衡来完成肺保护的作用。本研究的完成，可以阐明Tim-3/galectin-9信号通路参与调节肺移植术后急性排斥反应的免疫学机理，从而为临床肺移植术后的治疗提供新的靶点。