The Heterogeneity and Functional Roles of Dendritic Cells in Atherosclerosis: Origins, Subsets, and Therapeutic Implications

ABSTRACT: Atherosclerosis, a chronic inflammatory disease of the arterial wall, is driven by dysregulated immune responses. Dendritic cells (DCs), as central orchestrators of innate and adaptive immunity, accumulate in atherosclerotic lesions and critically influence disease progression through their roles in lipid metabolism, antigen presentation, and cytokine signaling. Recent advances in single-cell omics and genetic lineage tracing have unveiled the functional diversity of DC subsets, including conventional DCs (cDC1, cDC2), plasmacytoid DCs (pDCs), and monocyte-derived DCs (Mo-DCs), in shaping plaque inflammation, immune tolerance, and tissue repair. However, the mechanisms underlying DC heterogeneity, recruitment, and crosstalk with other immune and vascular cells remain incompletely understood. This review summarizes current knowledge on DC ontogeny, subset-specific functions, and their interplay with T cells, B cells, endothelial cells (ECs), and smooth muscle cells in Atherosclerosis. We also critically evaluate transgenic models for DC research and emerging DC-targeted therapies, including tolerogenic vaccines and nanoparticle-based strategies. Unresolved questions about spatial distribution, functional duality, and ontogenetic pathways are discussed to guide future investigations.