调控TSC1/Rictor诱导DCreg促进肾移植免疫耐受及其机制研究

树突状细胞（DC）诱导移植免疫耐受是器官移植的前沿和热点。结节性硬化复合物1（TSC1）通过抑制mTORC1促进DC的功能，我们发现敲除Rictor的DC可加速移植排斥反应，但是TSC1/Rictor轴对DC的调控机制不详。故本项目将探究TSC1调节DC功能对Rictor的依赖性，敲除DC的TSC1基因并过表达Rictor基因，诱导功能强大的调节性DC（TSC1 KO Rictor high DCreg），并将其过继转移到肾移植受体小鼠体内诱导免疫耐受。通过分析该DCreg对受体Tem、Treg的影响，供受体DC的cross-dressing，及其发挥功能对受体DC和Treg的依赖性等多角度探索其作用机制。该研究将揭示TSC1/Rictor通路对DC功能的调控机制，为诱导DCreg介导的移植免疫耐受提供新视角。

Dendritic cells (DC) induced transplant immune tolerance is the frontier and hotspot of organ transplantation. Tuberous sclerosis complex 1 (TSC1) can inhibit mTORC1 and promote the function of DC. Our previous study found that Rictor deficiency in DC could accelerate the transplant rejection, however, the regulation of TSC1/Rictor axis on DC function is unclear. Therefore, this project will explore the dependence of TSC1 on Rictor in regulating DC function. Knocking out TSC1 and overexpressing Rictor in DC to induce powerful regulatory dendritic cells (DCreg) which is entitled TSC1 KO Rictor high DCreg. Adoptive transfer of the TSC1 KO Rictor high DCreg into renal transplant recipient mice will induce immune tolerance. Analysis of the recipient’s Tem and Treg, donor and recipient DC's cross-dressing and DCreg's dependence on recipient DC and Treg to explore the mechanism of TSC1 KO Rictor high DCreg induced tolerance. This study will reveal the regulation mechanism of TSC1/Rictor pathway on DC function, and provides a new perspective for DCreg mediated transplant tolerance.