Single-cell RNA-Seq reveals CVI-mAb-induced Lyve1+M2-like macrophages reduce atherosclerotic plaque area in Apoe-/- mice

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 sub-populations 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.

Automated summary

In this study, the role of a specific subset of macrophages, Lyve1+ M2-like macrophages, in atherosclerosis was investigated using single-cell RNA sequencing analysis. It was found that these macrophages, detected mainly in mice treated with a high-fat diet and collagen VI monoclonal antibodies, showed distinct gene expression patterns and functions related to lipid metabolism. Further experiments demonstrated that transplantation of Lyve1+ M2-like macrophages could reduce plaque areas in mice with atherosclerosis.