单细胞 RNA 测序揭示 CVI-mAb 诱导的 Lyve1 M2 样巨噬细胞减少 Apoe 小鼠的动脉粥样硬化斑块面积。
Single-cell RNA-Seq reveals CVI-mAb-induced Lyve1 M2-like macrophages reduce atherosclerotic plaque area in Apoe mice.
机构信息
Department of Pathophysiology, Key Lab for Shock and Microcirculation Research of Guangdong, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
The Affiliated Nanhua Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
出版信息
Int Immunopharmacol. 2023 Mar;116:109794. doi: 10.1016/j.intimp.2023.109794. Epub 2023 Feb 1.
BACKGROUND
Atherosclerosis is a lipid imbalance-induced autoimmune disease. Macrophages participate in the development and progression of atherosclerosis. Although numerous studies have utilized single-cell RNA sequencing to identify the role of various macrophage phenotypes in atherosclerosis, the macrophage subpopulations that have therapeutic benefits against atherosclerosis are not fully understood.
METHODS
In this study, a single-cell RNA sequencing analysis was performed on the F4/80 macrophages of apolipoprotein E-deficient (Apoe) mice on a normal diet (ND), a high-fat diet (HFD), and a high-fat diet (HFD) with collagen VI monoclonal antibodies (CVI-mAb) treatment. A population of M2-like macrophages expressing the hyaluronan receptor Lyve1 was almost exclusively detectable in Apoe mice on an HFD with CVI-mAb treatment, compared with other groups. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns that distinguished this macrophage subset and uncovered its functions.
RESULTS
Lyve1 M2 macrophages appear to have specialized functions in lipid metabolism. Lyve1 M2-like macrophages were sorted via fluorescence- activated cell sorting (FACS) and adoptively transferred to Apoe mice fed an HFD.
CONCLUSION
Our result showed that Lyve1 M2 macrophages could reduce the plaque areas in Apoe mice.
背景
动脉粥样硬化是一种由脂质失衡引起的自身免疫性疾病。巨噬细胞参与动脉粥样硬化的发生和发展。尽管许多研究已经利用单细胞 RNA 测序来确定各种巨噬细胞表型在动脉粥样硬化中的作用，但对抗动脉粥样硬化具有治疗益处的巨噬细胞亚群尚未完全了解。
方法
在这项研究中，对正常饮食（ND）、高脂肪饮食（HFD）和用胶原 VI 单克隆抗体（CVI-mAb）治疗的载脂蛋白 E 缺陷（Apoe）小鼠的 F4/80 巨噬细胞进行了单细胞 RNA 测序分析。与其他组相比，在接受 CVI-mAb 治疗的 HFD 喂养的 Apoe 小鼠中，几乎可以特异性检测到表达透明质酸受体 Lyve1 的 M2 样巨噬细胞群体。差异基因表达和基因本体富集分析揭示了区分这种巨噬细胞亚群并揭示其功能的特定基因表达模式。
结果
Lyve1 M2 巨噬细胞似乎在脂质代谢中具有专门的功能。通过荧光激活细胞分选（FACS）对 Lyve1 M2 样巨噬细胞进行分选，并将其过继转移到喂食 HFD 的 Apoe 小鼠中。
结论
我们的结果表明，Lyve1 M2 巨噬细胞可以减少 Apoe 小鼠的斑块面积。
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