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Immune cells in atherosclerosis include T, B, natural killer (NK) and NKT cells, macrophages, monocytes, dendritic cells (DCs), neutrophils, and mast cells. Advances in single-cell RNA sequencing (sRNA-Seq) have refined our understanding of immune cell subsets. Four recent studies have used scRNA-Seq of immune cells in human atherosclerotic lesions and peripheral blood mononuclear cells (PBMCs), some including cell surface phenotypes revealed by oligonucleotide-tagged antibodies, which confirmed known and identified new immune cell subsets and identified genes significantly up-regulated in PBMCs from HIV+ subjects with atherosclerosis compared to PBMCs from matched HIV+ subjects without atherosclerosis. The ability of scRNA-Seq to identify cell types is greatly augmented by adding cell surface phenotype using antibody sequencing. In this review, we summarize the latest data obtained by scRNA-Seq on plaques and human PBMCs in human subjects with atherosclerosis.

Aims The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. Methods and results We transferred apoe-/-myd88+/+ or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88+/+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-γ. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells. Conclusion We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels.