Smooth Muscle Cell-Derived Interleukin-17C Plays an Atherogenic Role via the Recruitment of Proinflammatory Interleukin-17A+ T Cells to the Aorta.
Smooth Muscle Cell-Derived Interleukin-17C Plays an Atherogenic Role via the Recruitment of Proinflammatory Interleukin-17A+ T Cells to the Aorta.
复制标题
平滑肌细胞衍生的 Interleukin-17C 通过将促炎性 Interleukin-17A+ T 细胞募集至主动脉而发挥致动脉粥样硬化作用。
DOI：
10.1161/atvbaha.116.307892
复制
发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Galkina EV
中科院分区：
文献类型：
--
作者：
Butcher MJ;Waseem TC;Galkina EV
动脉粥样硬化的特征在于浸润的白细胞和血管细胞之间通过趋化因子和细胞因子网络的频繁通信。IL-17 C在动脉粥样硬化病变中是可检测的;然而，尚未检查该细胞因子的潜在参与。因此，我们试图研究IL-17 C在动脉粥样硬化中的作用。IL-17细胞因子的表达在Apoe−/− ApoE tas中进行了分析，并且IL 17 c表达升高。流式细胞术实验揭示了主动脉IL-17 C产生平滑肌细胞的主要群体。接下来，我们产生了Il 17 c-/-Apoe-/-小鼠，并证明与Apoe-/-对照组相比，喂食WD的Il 17 c-/-Apoe-/-主动脉和主动脉根部的动脉粥样硬化病变和胶原蛋白含量减少。平滑肌细胞和成纤维细胞是导致Il 17 c −/−Apoe−/−小鼠主动脉中Col 1A 1表达减少的主要原因。重要的是，IL-17 C处理的Apoe−/− Aptas在体外上调Col 1A 1表达。Il 17 c −/−Apoe−/−小鼠显示主动脉巨噬细胞、中性粒细胞、T细胞、Th 1和TcR成比例减少，而外周免疫组成无相应变化。对主动脉IL-17 A + TCRγδ T细胞和Th 17细胞的检查表明，与Apoe−/−小鼠相比，Il 17 c −/− Apoe −/−小鼠中这些亚群的百分比和数量明显减少。用IL-17 C处理的移植12周WD Apoe−/−血管导致多种血管趋化因子和细胞因子的诱导。Th 17细胞表现出向培养物Il 17 c −/−Apoe−/−平滑肌细胞上清液的迁移减弱，短期归巢实验显示，Th 17细胞向Il 17 c −/−Apoe−/−受体主动脉的募集减少。平滑肌细胞来源的IL-17 C通过支持Th 17细胞向动脉粥样硬化病变的募集而发挥促动脉粥样硬化作用。
Atherosclerosis is characterized by frequent communication between infiltrating leukocytes and vascular cells, through chemokine and cytokine networks. IL-17C is detectable within atherosclerotic lesions; however the potential involvement of this cytokine has not been examined. Thus we sought to investigate the role of IL-17C in atherosclerosis. The expression of IL-17 cytokines was profiled within Apoe−/− aortas and Il17c expression was elevated. Flow cytometry experiments revealed a major population of aortic IL-17C-producing smooth muscle cells. Next, we generated Il17c−/−Apoe−/− mice and demonstrated that atherosclerotic lesion and collagen content was diminished within WD-fed Il17c−/−Apoe−/− aortas and aortic roots in comparison to Apoe−/− controls. Smooth muscle cells and fibroblasts were mainly responsible for the reduced Col1A1 expression in the aorta of Il17c−/−Apoe−/− mice. Importantly, IL-17C treated Apoe−/− aortas upregulated Col1A1 expression ex vivo. Il17c−/−Apoe−/− mice displayed a proportional reduction in aortic macrophages, neutrophils, T cells, Th1, and Tregs, without corresponding changes in the peripheral immune composition. Examination of aortic IL-17A+ TCRγδ T cells and Th17 cells demonstrated a stark reduction in the percentage and number of these subsets within Il17c−/−Apoe−/− versus Apoe−/− mice. Explanted 12 week WD Apoe−/− aortas treated with IL-17C resulted in the induction of multiple vascular chemokines and cytokines. Th17 cells demonstrated attenuated migration towards supernatants from cultures Il17c−/−Apoe−/− smooth muscle cells and short-term homing experiments revealed diminished recruitment of Th17 cells to the aorta of Il17c−/−Apoe−/− recipients. Smooth muscle cell-derived IL-17C plays a pro-atherogenic role by supporting the recruitment of Th17 cells to atherosclerotic lesions.