MDSCs在动脉粥样硬化中的作用及机制

Atherosclerosis is a multifactorial disorder in which immune mechanisms play a leading role. Myeloid-derived suppressor cells (MDSCs) are the mainly immune suppressor cells and have a significant role in negative regulation of immune responses. In the previous study, we found that the frequency of CD14+HLA-DR-/low cells was significantly increased in patients with acute coronary syndrome (ACS), suggesting that MDSCs may be involved in the pathogenesis of AS. In this study, we intend to further explore the effects and mechanisms of MDSCs on T cells and the relationship between MDSCs and regulatory T (Treg) cells in order to clarify its role in ACS. To elucidate the role of MDSCs in AS of ApoE-/- mice, we will study the expression pattern of MDSCs and its subsets in the process of AS, and observe the process of AS and T cell responses after application Gr-1 specific antibody to block or adoptive transfer MDSCs to enhance its effects. Then, we will try to explain the mechanisms of negative regulation of immune responses of MDSCs by using the experimental techniques such as cell culture, Transwell and functional blocking. Through the study, it is expected to clarify the role of MDSCs in inflammation of AS.

免疫炎症在动脉粥样硬化（AS）的发生发展中起着主导作用。髓系来源的抑制性细胞（MDSCs）是机体内主要的免疫抑制细胞，起负向调节免疫应答的作用。我们的前期研究发现在急性冠脉综合征（ACS）患者中CD14+HLA-DR-/low的MDSCs显著增加，提示该细胞群可能参与AS的发病。本课题拟进一步分析ACS患者外周血中MDSCs对T细胞应答的影响和机制以及与调节性T细胞（Treg）的关系，阐明其在ACS中的作用；动态观察ApoE-/-小鼠AS进程中MDSCs及其亚群的表达规律，应用Gr-1抗体或过继传输MDSCs阻断或增强其效应，观察对AS进程和T细胞应答的影响，阐明其在AS炎症中的作用；通过体外分离培养、Transwell和功能阻断等实验技术，寻找MDSCs调节免疫应答的关键分子，阐明其发挥免疫调节作用的机制。通过本课题的研究，可望阐明MDSCs对AS免疫炎症的作用及机制。

免疫炎症在动脉粥样硬化（AS）的发生发展中起着主导作用。髓系来源的抑制性细胞（MDSCs）是机体内主要的免疫抑制细胞，起负向调节免疫应答的作用。我们的前期.研究发现在急性冠脉综合征（ACS）患者中CD14+HLA-DR-/low 的MDSCs 显著增加，提示该细胞群可能参与AS 的发病。本课题拟进一步分析ACS 患者外周血中MDSCs 对T 细胞应答的影响和机制以及与调节性T 细胞（Treg）的关系，阐明其在ACS 中的作用；动态观察ApoE-/-小鼠AS 进程中MDSCs 及其亚群的表达规律，应用Gr-1 抗体或过继传输MDSCs 阻断或增强其效应，观察对AS 进程和T 细胞应答的影响，阐明其在AS 炎症中的作用；通过体外分离培养、Transwell 和功能阻断等实验技术，寻找MDSCs 调节免疫应答的关键分子，阐明其发挥免疫调节作用的机制。通过本课题的研究，可望阐明MDSCs 对AS 免疫炎症的作用及机制。