IgG1 Is the Optimal Subtype for Treating Atherosclerosis by Inducing M2 Macrophage Differentiation, and Is Independent of the FcγRIIA Gene Polymorphism.
IgG1 Is the Optimal Subtype for Treating Atherosclerosis by Inducing M2 Macrophage Differentiation, and Is Independent of the FcγRIIA Gene Polymorphism.
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DOI：
10.3390/ijms24065932
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发表时间：
2023-03-21
影响因子：
5.6
通讯作者：
Zhao, Ming
中科院分区：
文献类型：
--
作者：
Duan, Rui;Liu, Yan;Tang, Dongmei;Lin, Run;Huang, Jinrong;Zhao, Ming
近年来，动脉粥样硬化被证实是一种自身免疫性疾病。然而，目前对FcγRIIA在动脉粥样硬化中的作用知之甚少。在此，我们试图探讨FcγRIIA基因分型与不同免疫球蛋白亚类治疗动脉粥样硬化疗效的关系。我们构建并生产了不同亚型的免疫球蛋白抗体和Fc工程抗体。在体外，我们观察了不同亚型的免疫球蛋白抗体和Fc工程抗体对患者和健康人CD14+单核细胞分化的影响。在体内，APOE−/−小鼠被喂以高脂饮食20周，并注射不同CVI-Ig G亚类或Fc工程抗体。用流式细胞仪检测单核细胞和巨噬细胞的极化程度。尽管与其他亚型相比，CVI-IgG4可减少MCP-1的释放，但在体外，IgG4不能通过诱导人单核/巨噬细胞分化而产生抗炎作用。此外，在动脉粥样硬化的治疗过程中，FcγRIIA基因多态性与不同的CVI-Ig G亚类无关。在体内，CVI-IgG1降低Ly6 Chigh单核细胞分化，促进M2巨噬细胞极化。我们还发现CVI-IgG1组IL-10的分泌上调，而V11和GAALIE对IL-10的分泌无明显影响。这些发现表明，IgG1是治疗动脉粥样硬化的最佳亚型，而CVI-IgG1可以诱导单核/巨噬细胞极化。总体而言，这些结果对治疗性抗体的开发具有重要意义。
In recent years, it has been established that atherosclerosis is an autoimmune disease. However, little is currently known about the role of FcγRIIA in atherosclerosis. Herein, we sought to investigate the relationship between FcγRIIA genotypes and the effectiveness of different IgG subclasses in treating atherosclerosis. We constructed and produced different subtypes of IgG and Fc-engineered antibodies. In vitro, we observed the effect of different subtypes of IgG and Fc-engineered antibodies on the differentiation of CD14+ monocytes from patients or healthy individuals. In vivo, Apoe−/− mice were fed a high-fat diet (HFD) for 20 weeks and administered injections of different CVI-IgG subclasses or Fc-engineered antibodies. Flow cytometry was used to assess the polarization of monocytes and macrophages. Although CVI-IgG4 reduced the release of MCP-1 compared to the other subtypes, IgG4 did not yield an anti-inflammatory effect by induction of human monocyte and macrophage differentiation in vitro. Furthermore, genetic polymorphisms of FcγRIIA were not associated with different CVI-IgG subclasses during the treatment of atherosclerosis. In vivo, CVI-IgG1 decreased Ly6Chigh monocyte differentiation and promoted M2 macrophage polarization. We also found that the secretion of IL-10 was upregulated in the CVI-IgG1-treated group, whereas V11 and GAALIE exerted no significant effect. These findings highlight that IgG1 is the optimal subtype for treating atherosclerosis, and CVI-IgG1 can induce monocyte/macrophage polarization. Overall, these results have important implications for the development of therapeutic antibodies.
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影响因子：
82.9
作者：
Ait-Oufella, H;Salomon, BL;Mallat, Z
通讯作者：
Mallat, Z
影响因子：
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通讯作者：
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作者：
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