BAFF-TACI信号通路介导的B细胞诱导树突状细胞免疫调节功能异常在慢性免疫性血小板减少症中的作用及免疫干预研究

Immune thrombocytopenia (ITP), as a common autoimmune disease, involves complicated pathological mechanisms. Previous studies on ITP focused on the dysregulated functions of just on or a few components of the immune system, which leads to the ignorance of the immune system as a whole. Recently, as the deepening of the interpretation about autoimmunity, mutual influence of immune cells has gained more and more attention. In this program, we will take the BAFF-TACI as the breakthrough point, which might help us in understanding the impact of dendritic cells induced by BCR-activated B cells (DCBCR-B) on the differentiation and homeostasis of subtypes of T helper cells in ITP under both in vitro and in vivo conditions. This program might shed light on new mechanisms of ITP pathogenesis as well as on novel targets that can be used for clinical treatment.

免疫性血小板减少症（immune thrombocytopenia，ITP）作为一种常见的自身免疫性疾病，其发病机制较为复杂。以往关于ITP 发病机制的研究多专注于一种或几种免疫细胞功能的异常，而忽视了将整个免疫系统作为一个认识整体。近年来，随着对自身免疫反应的了解逐渐深入，各种免疫细胞之间相互作用的异常在ITP发病中的作用日益受到重视。本项目中，我们拟以BAFF-TACI信号通路为切入点，从体外和体内两个方面探究ITP患者BCR活化的B细胞诱导的树突状细胞（dendritic cells induced by BCR-activated B cells，DCBCR-B）对各种T 辅助细胞亚群分化及稳态的影响极其具体作用机制，深入探索可能的免疫干预措施，为ITP尤其是难治性ITP的治疗提供新的思路。

Th1/Th2比例失衡在慢性ITP发病中起重要作用。恢复Th亚群平衡有助于纠正ITP免疫紊乱。近年来，随着对自身免疫反应的了解逐渐深 入，各种免疫细胞之间相互作用的异常在ITP发病中的作用日益受到重视。课题申请者最新发现，ITP患者单核细胞来源的树突状细胞存在TACI表达减低，BAFF表达异常升高，上述异常在Th1/Th2极化异常过程中有促进作用。结合既往项目负责人成功构建血小板抗原载荷树突状细胞体外扩增诱导体系的经验，本研究深入探讨了BAFF/TACI作用下，经过活化B细胞诱导的树突状细胞（DCBCR-B）在表型、功能以及其对Th1/Th2失衡的纠正作用和具体机制。并进一步利用基因干扰、特异性抗体阻断剂干预其关键作用的传导分子，研究其对于上述树突状细胞免疫调节功能的影响。本课题组同时探讨了体外诱导扩增DCBCR-B并进行体内回输对于重建ITP模型鼠Th1/Th2亚群平衡的可能性。以上研究从新的角度为ITP患者，尤其是复发及难治ITP患者的治疗提供了新的思路。