Dendritic Cells and T Cells, Partners in Atherogenesis and the Translating Road Ahead

Abstract

Atherosclerosis is a chronic process associated with arterial inflammation, the accumulation of lipids, plaque formation in vessel walls, and thrombosis with late mortal complications such as myocardial infarction and ischemic stroke. Immune and inflammatory responses have significant effects on every phase of atherosclerosis. Increasing evidence has shown that both innate and adaptive "arms" of the immune system play important roles in regulating the progression of atherosclerosis. Accumulating evidence suggests that a unique type of innate immune cell, termed dendritic cells (DCs), play an important role as central instigators, whereas adaptive immune cells, called T lymphocytes, are crucial as active executors of the DC immunity in atherogenesis. These two important immune cell types work in pairs to establish pro-atherogenic or atheroprotective immune responses in vascular tissues. Therefore, understanding the role of DCs and T cells in atherosclerosis is extremely important. Here, in this review, we will present a complete overview, based on existing knowledge of these two cell types in the atherosclerotic microenvironment, and discuss some of the novel means of targeting DCs and T cells as therapeutic tactics for the treatment of atherosclerosis.

Dendritic cell-mediated chronic low-grade inflammation is regulated by the RAGE-TLR4-PKCβ1 signaling pathway in diabetic atherosclerosis

“…A previous study reported that a lack of DCs in mice could significantly reverse the progression of atherosclerotic plaques (Durpes et al 2015). In further exploration of the subsets of DCs (Sun et al 2020), it was found that CD11b + DC (Stoneman et al 2007;Busch et al 2014;Gao et al 2016;Rombouts et al 2016) and CCL17 + DC (Rader and Daugherty, 2008;Weber et al 2011) subsets have the effect of promoting atherosclerosis, and further exploration under more experimental conditions will provide multi-dimensional evidence. Whether CD103 + DCs (Choi et al 2011;Li et al 2017;Clement et al 2018) and plasmacytoid DCs (Daissormont et al 2011;Macritchie et al 2012) play pro-atherosclerotic or anti-atherosclerotic roles is controversial, which may depend on animal strains, different pathological models and other conditions.…”

Inflammatory Markers Related to Innate and Adaptive Immunity in Atherosclerosis: Implications for Disease Prediction and Prospective Therapeutics

“…T cells expressing the surface marker of CD8 are involved in the recognition of antigens expressed by the major histocompatibility complex (MHC) class I. CD8 + T cells kill the target cells by triggering apoptosis in the target cells. 81 Several chemokines released in the atherosclerotic lesion milieu are involved in the recruitment of the CD8 + T cells, which may then stimulate apoptosis in other immune cells and VSMCs, resulting in the development of lesions and related adverse complications. 82 , 83 One of the functions of the natural killer (NK) T (NKT) cells is to recognize lipid antigens presented by CD1 molecules on several cells.…”

Single-Cell RNA-Seq Reveals a Crosstalk between Hyaluronan Receptor LYVE-1-Expressing Macrophages and Vascular Smooth Muscle Cells

“…In line with the observed gene expression profile of cluster 1, the GO term enrichment analysis revealed signaling pathways linked to T-cell activation, the positive regulation of cell adhesion, cytokine production, cell-to-cell adhesion, and leukocyte migration, as well as antigen processing and presentation via MHC class II (Figure S4B). This indicates that cluster 1 is an important population involved in antigen presentation and T-cell activation in the atherosclerotic plaques [44]. Cluster 2 exhibited a gene expression profile of macrophages as shown by the expression of Ednrb, Fcna, Retnl, and Cd209f, as well as genes that are typical for resident macrophages (Lyve1 and FCGR1A (CD64)) [5] (Figures 2G and S3).…”