Functional specialization of dendritic cell (DC) subsets: implications for precision vaccinology

Dendritic cells (DCs) bridge innate sensing and adaptive immunity. Their functional heterogeneity derives from fundamental differences among DC subsets in ontogeny, tissue distribution, receptor repertoires, and antigen-processing pathways, establishing a specialized “division of labor” in antigen presentation, encompassing classical major histocompatibility complex (MHC) II-restricted presentation of exogenous antigens, MHC I-restricted presentation of endogenous antigens, and differences in the efficiency and preference of antigen cross-presentation. These subset-intrinsic features enable DCs to selectively instruct naïve T cells toward cytotoxic immunity, helper lineage differentiation, or immune tolerance. Recent advances reveal previously unappreciated dimensions of DC specialization. Type 1 conventional dendritic cells (cDC1s) not only excel in cross-presentation but also shape tumor immunogenicity through CLEC9A (also known as DNGR-1)-mediated recognition of F-actin-associated neoantigens, driving immune editing. Type 2 conventional dendritic cells (cDC2s) orchestrate lymph node dynamics-recruiting innate effectors to form transient “immune firewalls” and subsequently restoring tissue architecture for efficient T cell priming. In this review, we delineate how subsets-specific differences dictate specialized functions and shape immune outcomes. This review discusses DC subset biology from the perspective of veterinary vaccine research, with attention to both conserved mechanisms and species differences. We also summarize how DC-targeted delivery may be considered in veterinary precision vaccinology. Insights from large-animal models offer unique opportunities to validate next-generation vaccines against major animal diseases while informing human vaccine design through bidirectional cross-species translation.