主动脉瓣膜钙化是慢性炎症性疾病，严重危害人类健康，其发病机制不清楚。申请人前期通过高脂饮食喂养成功构建ApoE-/-小鼠主动脉瓣膜钙化模型，借助单细胞和TCR repertoire联合测序,首次发现ApoE-/-小鼠钙化主动脉瓣膜中存在组织特异性T淋巴细胞浸润，推测其分泌的IL1β与主动脉瓣膜间质细胞（VIC）表面受体IL1R1存在相互作用关系。本项目拟收集小鼠和人主动脉瓣膜组织，研究钙化瓣膜组织特异性T细胞，探索其细胞功能及克隆表达特征，继而通过细胞共培养及构建基因敲除动物模型的方法，揭示组织特异性T淋巴细胞调控瓣膜间质细胞受体IL1R1介导主动脉瓣膜钙化。本项目的实施，将有助于我们从组织特异性淋巴细胞的全新角度阐明主动脉瓣膜钙化病理生理机制，为临床防治主动脉瓣膜钙化提供潜在靶点。

Aortic valve calcification is a chronic inflammatory disorder that seriously harms human health. However, the mechanism of aortic valve calcification remains unclear. The applicant successfully constructed aortic valve calcification model in ApoE-/- mice fed by high-fat diet. Through single cell RNA sequencing and TCR repertoire sequencing, our previous study firstly confirmed that tissue-specific T-lymphocytes could be found in calcified aortic valve of ApoE-/- mice, and speculated there was cell-cell interaction IL1β-IL1R1 between T cells and aortic valve interstitial cells (VIC). This project intends to collect mice and human calcified aortic valves, and explore the function and clonal expression characteristics of tissue-specific T cells in vivo. Further verified by cells co-culture and gene knockout animal model, the mechanism of tissue-specific T cells mediated-aortic valve calcification through the interstitial cell receptor IL1R1 will be revealed. The implementation of this project will help us elucidate the pathophysiological mechanism of aortic valve calcification from the new perspective of tissue-specific lymphocytes, and provide potential targets for clinical intervention, diagnosis and treatment of aortic valve calcification.