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.

Keywords

Dendritic cells / Atherosclerotic plaques / Vascular cells / Mouse models

Acknowledgments

We thank all the members of GRIS in Xinxiang Medical University.

Author Contributions

Conceptualization, T.L. and Y.L.; Methodology, T.L.; Software, T.L.; Validation, L.L.; Investigation, J.Q. and D.L.; Writing—Original Draft Preparation, T.L.; Writing—Review & Editing, L.Z. and Y.L.; Visualization, T.L.; Funding Acquisition, Y.L. and T.L.

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were generated or analyzed in support of this review. All data discussed or cited are available from the original publications provided in the reference list.

Funding

This work was supported by National Natural Science Foundation of China (82301972), Science and Technology Department of Henan Province (242102310030) and 111 program (No. D20036).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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