Immune landscape and regulatory mechanisms in human atherosclerotic coronary plaques: Evidence from single-cell and bulk transcriptomics

Atherosclerosis is a chronic immuno-inflammatory disease, however, the immune landscape and regulatory mechanisms have not been clear. We detected seven principal immune cell clusters with distinct phenotypic and spatial characteristics using single-cell RNA-sequencing of aortic immune cells from patients with acute coronary syndrome and stable angina pectoris. Then we acquired 265 differentially expressed immune-related genes and the high scores were mainly found in T cells and monocytes, which were differentially regulated in atherosclerotic coronary plaques. The CCL signaling pathway was the most relevant pattern in the T cells and CCL5-CCR1 and CCL5-CCR5 ligand-receptor pairs played a vital role in the CCL signaling pathway. Further comparative analysis indicated MCH-I signaling was the most relevant pattern in the T cells and HLA ligand-related ligand-receptor pairs played a vital role. Functional analysis of the single-cell and bulk transcriptomics pointed to multiple pathways, such as antigen presentation and immune response. Nineteen common differentially expressed immune-related genes were found in both immune cells and the human peripheral blood mononuclear cells. Nine common differentially expressed transcription factors were differentially expressed in both T cell and monocyte clusters from the coronary plaques and human peripheral blood mononuclear cells and the network demonstrated that CEBPB might play an essential role in the transcriptional regulation of atherosclerosis as a hub transcription factor. The definition of immune cell diversity and heterogeneity by single-cell level analysis of aortic immune cell subsets not only unveils cell-type-specific pathways and new immune mechanisms but also discovers the functional correlation of immune cells in human atherosclerosis. Our findings provide great promise for the discovery of novel molecular mechanisms and precise therapeutic targets for atherosclerosis.