Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, China.
J Immunol. 2010 Nov 15;185(10):5820-7. doi: 10.4049/jimmunol.1000116. Epub 2010 Oct 15.
Considerable evidence supports that the CD4(+) T cell-mediated immune response contributes to the development of atherosclerotic plaque. However, the effects of Th17 cells on atherosclerosis are not thoroughly understood. In this study, we evaluated the production and function of Th17 and Th1 cells in atherosclerotic-susceptible ApoE(-/-) mice. We observed that the proportion of Th17 cells, as well as Th1, increased in atherosclerotic ApoE(-/-) mice compared with nonatherosclerotic wild-type littermates. In ApoE(-/-) mice with atherosclerosis, the expression of IL-17 and retinoic acid-related orphan receptor γt was substantially higher in the arterial wall with plaque than in the arterial wall without plaque. Increased Th17 cells were associated with the magnitude of atherosclerotic plaque in ApoE(-/-) mice. Importantly, treatment of ApoE(-/-) mice with neutralizing anti-IL-17 Ab dramatically inhibited the development of atherosclerotic plaque, whereas rIL-17 application significantly promoted the formation of atherosclerotic plaque. These data demonstrate that Th17 cells play a critical role in atherosclerotic plaque formation in mice, which may have implications in patients with atherosclerosis.
大量证据表明，CD4(+) T 细胞介导的免疫应答有助于动脉粥样硬化斑块的形成。然而，Th17 细胞对动脉粥样硬化的影响尚未得到充分了解。在本研究中，我们评估了易患动脉粥样硬化的 ApoE(-/-)小鼠中 Th17 和 Th1 细胞的产生和功能。我们观察到，与非动脉粥样硬化的野生型同窝仔相比，动脉粥样硬化的 ApoE(-/-)小鼠中 Th17 细胞和 Th1 的比例增加。在有动脉粥样硬化的 ApoE(-/-)小鼠中，斑块部位动脉壁中 IL-17 和维甲酸相关孤儿受体 γt 的表达明显高于无斑块部位。Th17 细胞的增加与 ApoE(-/-)小鼠中动脉粥样硬化斑块的程度有关。重要的是，用中和抗 IL-17 Ab 治疗 ApoE(-/-)小鼠可显著抑制动脉粥样硬化斑块的形成，而 rIL-17 的应用则可显著促进动脉粥样硬化斑块的形成。这些数据表明，Th17 细胞在小鼠动脉粥样硬化斑块形成中发挥关键作用，这可能对动脉粥样硬化患者具有重要意义。
