IL-17A经Act1-Beclin1通路调控巨噬细胞自噬及对动脉粥样硬化斑块易损性的作用

Autophagy is a catabolic cellular process that is both homeostatic and stress adaptive. Recent studies reveal the crucial effect of autophagy in atherosclerotic plaque stability，especially the macrophage autophagy. Our preliminary studies have confirmed that proinflammatory cytokine IL-17A may promote atherosclerotic plaque formation and plaque vulnerability. At the same time, we found IL - 17A raised Beclin1 and induced macrophage autophagy. However, the underlining mechanism remains unclear. Based on the previous researches, this study will clerify whether IL-17A regulates autophagy by Act1- Traf6-Beclin1-PI3KCIII axis, and investigate the effect of IL-17A on macrophage autophagy and the possible mechanisms. The research further define that the role of IL-17-modulated autophagy in atherosclerotic plaque vulnerability in vitro and in vivo. This research will contribute to reveal the novel mechanisms for IL-17-modulated autophagy in atherosclerotic plaque stability, providing a new strategy for prevention and treatment of atherosclerosis.

自噬是一种保守的调控细胞代谢的方式，为细胞自身代谢提供能量并更新细胞器，从而维持细胞自身稳态。近来研究发现自噬对动脉粥样硬化的斑块稳定性具有重要的影响，尤其巨噬细胞自噬的作用更为重大。我们前期研究证实细胞因子IL-17A可以促进动脉粥样硬化斑块形成并增加易损性，同时发现IL-17A可以上调自噬相关蛋白Beclin1，促进巨噬细胞自噬。目前其确切调控机制尚不明确。本课题拟在前期研究的基础上，以Act1-Traf6-Beclin1-PI3KCIII轴为切入点，深入探讨IL-17A对巨噬细胞自噬的调控作用及机制，进一步采用体内外结合的研究策略，明确IL-17A介导的巨噬细胞自噬对动脉粥样硬化斑块易损性的作用，为维护动脉粥样硬化斑块稳定性提供新的思路和防治策略。