OBJECTIVE By binding to its high-affinity receptor FcεR1, IgE activates mast cells, macrophages, and other inflammatory and vascular cells. Recent studies support an essential role of IgE in cardiometabolic diseases. Plasma IgE level is an independent predictor of human coronary heart disease. Yet, a direct role of IgE and its mechanisms in cardiometabolic diseases remain incompletely understood. Approach and Results: Using atherosclerosis prone Apoe-/- mice and IgE-deficient Ige-/- mice, we demonstrated that IgE deficiency reduced atherosclerosis lesion burden, lesion lipid deposition, smooth muscle cell and endothelial cell contents, chemokine MCP (monocyte chemoattractant protein)-1 expression and macrophage accumulation. IgE deficiency also reduced bodyweight gain and increased glucose and insulin sensitivities with significantly reduced plasma cholesterol, triglyceride, insulin, and inflammatory cytokines and chemokines, including IL (interleukin)-6, IFN (interferon)-γ, and MCP-1. From atherosclerotic lesions and peritoneal macrophages from Apoe-/-Ige-/- mice that consumed an atherogenic diet, we detected reduced expression of M1 macrophage markers (CD68, MCP-1, TNF [tumor necrosis factor]-α, IL-6, and iNOS [inducible nitric oxide synthase]) but increased expression of M2 macrophage markers (Arg [arginase]-1 and IL-10) and macrophage-sterol-responsive-network molecules (complement C3, lipoprotein lipase, LDLR [low-density lipoprotein receptor]-related protein 1, and TFR [transferrin]) that suppress macrophage foam cell formation. These IgE activities can be reproduced in bone marrow-derived macrophages from wild-type mice, but muted in cells from FcεR1-deficient mice, or blocked by anti-IgE antibody or complement C3 deficiency. CONCLUSIONS IgE deficiency protects mice from diet-induced atherosclerosis, obesity, glucose tolerance, and insulin resistance by regulating macrophage polarization, macrophage-sterol-responsive-network gene expression, and foam cell formation.

中文翻译：

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IgE通过影响巨噬细胞极化，巨噬细胞蛋白网络和泡沫细胞形成而有助于动脉粥样硬化和肥胖。

目的通过结合其高亲和力受体FcεR1，IgE激活肥大细胞，巨噬细胞以及其他炎症和血管细胞。最近的研究支持IgE在心脏代谢疾病中的重要作用。血浆IgE水平是人类冠心病的独立预测因子。然而，IgE及其在心血管代谢疾病中的作用的直接作用仍不完全清楚。方法和结果：使用易患动脉粥样硬化的Apoe-/-小鼠和IgE缺乏的Ige-/-小鼠，我们证明了IgE缺乏减少了动脉粥样硬化的病变负担，病变脂质沉积，平滑肌细胞和内皮细胞含量，趋化因子MCP（单核细胞趋化蛋白） ）-1表达和巨噬细胞积累。IgE缺乏症还会降低体重增加，并增加葡萄糖和胰岛素敏感性，同时血浆胆固醇，甘油三酸酯，胰岛素和炎性细胞因子和趋化因子（包括IL（白介素）-6，IFN（干扰素）-γ和MCP-1）显着降低。从食用动脉粥样化饮食的Apoe-/-Ige-/-小鼠的动脉粥样硬化病变和腹膜巨噬细胞中，我们检测到M1巨噬细胞标志物（CD68，MCP-1，TNF [肿瘤坏死因子]-α，IL-6，和iNOS [诱导型一氧化氮合酶]），但M2巨噬细胞标志物（Arg [精氨酸酶] -1和IL-10）和巨噬细胞-甾醇响应网络分子（补体C3，脂蛋白脂肪酶，LDLR [低密度脂蛋白]受体]相关蛋白1和TFR [转铁蛋白]）抑制巨噬细胞泡沫细胞的形成。这些IgE活性可以在野生型小鼠的骨髓巨噬细胞中复制，但在FcεR1缺陷型小鼠的细胞中却被静音，或者被抗IgE抗体或补体C3缺陷所阻断。结论IgE缺乏症通过调节巨噬细胞极化，巨噬细胞-甾醇反应网络基因表达和泡沫细胞形成，保护小鼠免受饮食诱导的动脉粥样硬化，肥胖，葡萄糖耐量和胰岛素抵抗。