Takayasu动脉炎是我国最常见进行性自身免疫性大血管炎，既是临床疑难杂症，也是重大治疗难题。T细胞在Takayasu动脉炎发病中发挥重要致病作用；我们前期研究发现mTOR活性异常升高是患者致病性T细胞分化和功能的重要因素，靶向抑制T细胞mTOR活性具有重要转化价值；但其T细胞mTOR活性异常的机制仍不清楚。Notch是调节T细胞分化和功能的重要分子，可调控mTOR活性；该项目在已有研究基础上，深入发掘Takayasu动脉炎患者T细胞Notch信号特征性改变及其在T细胞分化和功能以及mTOR活性异常升高中的作用，结合免疫共沉淀和质谱分析探讨Notch对mTOR蛋白翻译后修饰以及亚细胞定位的可能影响，同时以人源化Takayasu疾病模型评价靶向调控Notch及其关键作用分子的转化价值。项目研究不仅有助于深入理解Takayasu动脉炎发病机制，更可拓展疾病靶向治疗新分子，推动研究成果转化。

Takayasu arteritis, a progressive autoimmune large vessel vasculitis, is the most common type in clinical cases, serving as an obstacle in clinical management. While T cells play an important role in driving Takayasu arteritis, our recent study identified mTOR hyperactivity unpinning the differentiation and function of pathogenic T cells in patients. However, the mechanisms underlying mTOR hyperactivity still remains unclear. Notch is critical for determining T cell fate and regulating mTOR activity. Herein, we aim to explore the Notch expression and function in Takayasu T cells, studying its potential role in T cell differentiation and function and in the mTOR hyperactivity. Specifically, we will investigate the direct effect of Notch signaling on mTOR activity, characterizing the post-translation modification and sub-cellular localization of mTOR. Of note, we will established the humanized Takayasu disease model and evaluate the translation values of targeting Notch signaling. This project will not only further our understanding of the parthenogenesis of Takayasu arteritis, but also will provide novel therapeutic targets for this disease.