Th1、Th17细胞增高及Th2细胞降低在慢性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。TIGIT+CD4+CD25+ Foxp3+ Tregs是一群表型和功能特异的Treg亚型，其可显著抑制naive T细胞向Th1、Th17细胞分化，并分泌sFGL2促进Th2细胞分化。课题申请者最新发现，ITP患者外周血TIGIT+ Tregs比例明显降低，结合既往课题组利用CD4+CD25- T细胞成功诱导CD4+CD25+ Foxp3+ Tregs经验，本研究拟体外诱导扩增并纯化TIGIT+ Tregs，观察其离体培养状态对慢性ITP患者Th亚群分化增殖影响，同时探讨纯化回输TIGIT+ Tregs重建ITP模型鼠Th亚群平衡的可能性。进一步利用基因干扰或特异性抗体阻断技术，干预TIGIT+ Tregs关键信号传导分子，研究其对Th亚群平衡重建的影响，为ITP治疗提供新思路

It has been well established that elevated Th1, Th17 cells and decreased Th2 frequencies were involved in the pathophysiological process of chronic ITP. Restoration of Th subset balance could exert beneficial effects on the correction of immune dysregulation. TIGIT+CD4+CD25+ Foxp3+ Tregs were a newly identified Treg cell subset with distinct phenotype and function. TIGIT+ Tregs could inhibit differentiation of Th1 and Th17 cells, but promote Th2 cell differentiation by secretion of sFGL2. In patients with active ITP, we recently observed that frequencies of peripheral TIGIT+ Tregs were decreased. Based on our previous report about ex vivo induction of CD4+CD25+ Foxp3+ Tregs from CD4+CD25- T cells, we intend to expand and purify TIGIT+ Tregs in vitro, and explore their effect on the differentiation and proliferation of different Th subsets derived from chronic ITP patients. Also, we plan to evaluate the possibility of reestablishing Th subset balance in murine model of ITP by adoptive transfer of in vitro-expanded TIGIT+ Tregs, and investigate the underlying mechanisms by interfering with several crucial signaling molecules using RNA interference or antibody blockade technology. Conduction of the project will help to develop novel strategies for the management of ITP.