IL-35-Treg 细胞的分化发育及功能学研究

调节性T细胞（Treg）活化分化过程对维持自身免疫稳态至关重要，效应性Treg可分泌IL-10、IL-35等可溶性抑制性细胞因子，行使区域免疫抑制功能。我们的前期结果显示分泌IL-35的IL-35-Treg和分泌IL-10的Blimp1-Treg是两群完全独立的效应性Treg亚群，在机体免疫耐受中可能发挥不同的作用。目前IL-35-Treg的分化发育并不清楚，本项目拟利用已构建的35EbiT-Blimp1-GFP双报告基因小鼠，通过转录组测序分析比较这两群效应性Treg在转录水平的差异，获得IL-35-Treg的特异性转录谱，结合转录因子筛选、体外过表达和CRISPR/Cas9技术，揭示IL-35-Treg 的分化发育规律，探索IL-35-Treg和Blimp1-Treg的免疫学功能。该研究将深化我们对Treg免疫抑制机制的认识，可能为多种自身免疫疾病、感染性疾病及癌症等提供新的治疗策略。

Treg activation and functional specialization play critical role in immune self-tolerance. The immunosuppressive cytokines TGF-beta, IL-10 and IL-35 have been implicated in regulatory T cell function to suppress local immunity through a combination of bystander suppression and infectious tolerance. Our preliminary results demonstrated the IL-35 secreting Treg (IL-35-Treg), was a distinct Treg lineage from the Blimp-1 dependent IL-10 producing subset (Blimp-1-Treg). Here, we propose to determine the transcriptional regulation of IL-35-Treg by comparing the mRNA profiling of IL-35-Treg and Blimp-1-Treg, in combining with in vitro reporter screening, retrovirus based overexpresion, as well as CRISPR/Cas9 knockout experiment, we hope to elucidate the detailed molecular mechanism in controlling IL-35-Treg generation. This study will provide a better understanding of immunosuppressive mechanism of Treg, and might have important implications in both autoimmune pathogenesis and the tumor therapy.