Exogenous interleukin 37 ameliorates atherosclerosis via inducing the Treg response in ApoE-deficient mice.
Exogenous interleukin 37 ameliorates atherosclerosis via inducing the Treg response in ApoE-deficient mice.
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外源性白细胞介素 37 通过诱导 ApoE 缺陷小鼠的 Treg 反应改善动脉粥样硬化
DOI：
10.1038/s41598-017-02987-4
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发表时间：
2017-06-12
影响因子：
4.6
通讯作者：
Zeng Q
中科院分区：
文献类型：
--
作者：
Ji Q;Meng K;Yu K;Huang S;Huang Y;Min X;Zhong Y;Wu B;Liu Y;Nie S;Zhang J;Zhou Y;Zeng Q
我们前期的研究表明白细胞介素（IL）-37参与了动脉粥样硬化的形成。在本研究中，胫前动脉收集糖尿病患者和对照组。组织病理学分析显示IL-37在人动脉粥样硬化斑块中过表达。人动脉粥样硬化斑块中多种细胞包括巨噬细胞、血管平滑肌细胞、内皮细胞和T淋巴细胞表达IL-37。将ApoE −/−小鼠分为对照组和重组人IL-37处理组。IL-37治疗导致巨噬细胞和CD4 + T淋巴细胞显著减少，动脉粥样硬化斑块中VSMC和胶原蛋白显著增加，导致动脉粥样硬化斑块尺寸减小。此外，IL-37处理可调节CD4 + T淋巴细胞活性，包括减少辅助性T细胞1型（Th1）和Th17细胞，增加调节性T细胞（Treg），并抑制体内和体外树突状细胞的成熟。此外，用抗IL-10受体单克隆抗体治疗废除了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应答来改善动脉粥样硬化。IL-37可能成为一种新的防治动脉粥样硬化疾病的药物。
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 bothin vivoandin 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.