IL-35在动脉粥样硬化进程中的作用和机制研究

We found that the plasma interleukin-35(IL-35) levels in patients with coronary artery disease were siginificantly lower than those in the control group. Our preliminary study showed that recombinant mouse IL-35 treatment of ApoE-/- mice ameliorated atherosclerosis development. Therefore, we hypothesized that IL-35 may become a novel target for the treatment of atherosclerosis. The change in IL-35 production and the development of atherosclerosis will be dynamically investigated in this sstudy. In addition, different approaches will be used to up-regulate or abolish the effect of IL-35 to clarify the exact role of IL-35 in atherosclerosis. This study is deem to discover novel experimental evidence for the impaired immune function and regulatory mechanism in atherosclerosis, providing a potential therapeutic approach for the treatment of atherosclerosis.

课题组前期研究发现，冠心病患者血浆IL-35水平显著降低。预实验表明，重组IL-35可显著延缓动脉粥样硬化（AS）进程。因此，我们提出IL-35负向调节AS进程的假说。本研究将动态观察AS进程和IL-35水平变化，并采用上调或阻断IL-35、过继转输iTr35等方法进行干预，阐明IL-35负向调节AS的机制。本研究的顺利进行，可望为AS进程免疫功能的受损及调控机制提供新的实验依据，并提出以IL-35为靶点恢复免疫稳态、防治动脉粥样硬化的新思路，具有一定的理论价值和创新性。

动脉粥样硬化是一种由T细胞介导的慢性炎症性疾病。T细胞亚群功能的失衡在动脉粥样硬化进程中发挥了重要作用。本研究将新型细胞因子IL-35与CD4+T细胞亚群、动脉粥样硬化二者结合起来，拟阐IL-35调控动脉粥样硬化的新机制。.在为期四年的研究中，我们发现IL-35抑制动脉粥样硬化进程中不仅诱导了调节性T细胞占优势的免疫反应，还抑制了Th17型免疫反应，但是敲除p35亚基不仅动脉粥样硬化进程得到改善，同时Th1型免疫反应受到抑制，而Th2型免疫反应活性上调，这可能跟p35敲除同时取消了IL-12的促动脉粥样硬化效应有关。