Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing, 100029, China.
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Sci Rep. 2017 Jun 12;7(1):3310. doi: 10.1038/s41598-017-02987-4.
Our previous study indicated that interleukin (IL)-37 is involved in atherosclerosis. In the present study, Anterior tibial arteries were collected from diabetes patients and controls. A histopathological analysis showed that IL-37 was over-expressed in human atherosclerotic plaques. Many types of cells including macrophages, vascular smooth muscle cells (VSMCs), endothelial cells and T lymphocyte expressed IL-37 in human atherosclerotic plaques. ApoE-/- mice were divided into a control group and a recombinant human IL-37-treated group. The IL-37 treatment resulted in a significant decrease in macrophages and CD4+ T lymphocytes and a substantial increase in VSMCs and collagen in atherosclerotic plaques, resulting in a reduction in atherosclerotic plaque size. Furthermore, the IL-37 treatment modulated the CD4+ T lymphocyte activity, including a decrease in T helper cell type 1 (Th1) and Th17 cells and an increase in regulatory T (Treg) cells, and inhibited the maturity of dendritic cells both in vivo and in vitro. In addition, treatment with anti-IL-10 receptor monoclonal antibody abrogated the anti-atherosclerotic effects of IL-37. These data suggest that exogenous IL-37 ameliorates atherosclerosis via inducing the Treg response. IL-37 may be a novel therapeutic to prevent and treat atherosclerotic disease.
我们之前的研究表明白细胞介素（IL）-37 参与动脉粥样硬化。在本研究中，从前壁胫骨动脉收集糖尿病患者和对照者的样本。组织病理学分析表明，IL-37 在人动脉粥样硬化斑块中过度表达。在人动脉粥样硬化斑块中，包括巨噬细胞、血管平滑肌细胞（VSMC）、内皮细胞和 T 淋巴细胞在内的许多类型的细胞都表达 IL-37。ApoE-/- 小鼠分为对照组和重组人 IL-37 治疗组。IL-37 治疗导致巨噬细胞和 CD4+T 淋巴细胞显著减少，VSMC 和胶原显著增加，导致动脉粥样硬化斑块大小减少。此外，IL-37 治疗调节 CD4+T 淋巴细胞活性，包括减少辅助性 T 细胞 1（Th1）和 Th17 细胞，增加调节性 T（Treg）细胞，并在体内和体外抑制树突状细胞的成熟。此外，用抗白细胞介素 10 受体单克隆抗体治疗消除了 IL-37 的抗动脉粥样硬化作用。这些数据表明，外源性 IL-37 通过诱导 Treg 反应改善动脉粥样硬化。IL-37 可能是预防和治疗动脉粥样硬化疾病的一种新的治疗方法。
