新型T细胞亚群Th9/IL-9在动脉粥样硬化进程中的作用和机制研究

动脉粥样硬化（AS）的发生和进展与T细胞介导的免疫炎症密切相关。Th9细胞是一种新发现的T细胞亚群，以特异性分泌白介素9（IL-9）得名，主要通过激活STAT1/3/5等通路介导炎症反应。我们前期研究发现：冠心病急性冠脉综合征患者外周血Th9/IL-9水平升高，ApoE-/-自发性AS小鼠给予外源性IL-9后斑块面积显著增大，均提示IL-9具有促AS作用，其具体效应机制有待进一步阐明。本研究试图探讨：阻断和增强Th9/IL-9效应对AS进程（斑块形成和自发性斑块不稳定）的影响；肥大细胞在IL-9诱导自发性斑块不稳定中的作用；AS自身抗原对Th9细胞分化的影响；IL-9对AS相关细胞生物学功能的影响。最终全面深入的阐明Th9/IL-9在AS进程中的作用和分子机制，为AS炎症的靶向治疗提供新的理论基础和实验依据。

It has been demonstrated that T-cell mediated inflammation is associated with atherosclerosis. Th9 cells that secrete IL-9 mainly mediate the local inflammation through STAT1/3/5 pathway. Our recent study demonstrated that the level of Th9/IL-9 elevated in the peripheral blood of patients with acute coronary syndrome and the plaque area increased in ApoE-/- mice after administrated by exogenous IL-9, which indicating an important role of IL-9 in promoting atherosclerosis. However, the definite effects and mechanisms were to be elucidated. We planned to clarify the effects of Th9/IL-9 on atherosclerosis by three steps as follows: firstly, we intend to explore the effects of Th9/IL-9 blockade or enhancement on the development of atherosclerosis (formation of plaque and spontaneous rupture of the plaque). Secondly, we will detect the role of mast cells in IL-9 inducing plaque vulnerability. Thirdly, we will detect the effects of atherosclerosis-associtatied autoantigen on the differentiation of Th9 cell and the effects of IL-9 on the function of several atherosclerosis related cells. Our research is aimed at elucidating the effects and mechanisms of a new subset of T cell-Th9 cell in atherosclerosis and offering new knowledge and experimental proof for the targeted therapy of atherosclerosis.