Dendritic Cells: key controllers of lymphoid tissue organization

Dendritic cells (DCs) are highly efficient antigen-presenting cells that play a central role in inducing and controlling immune responses. Beyond their role in antigen presentation and in orchestrating lymphocyte activities, DCs also contribute to the spatial and functional organization of lymphoid structures, including both secondary and tertiary lymphoid organs, acting at different levels during both lymphoid tissue neogenesis and their maintenance. DCs can facilitate lymphoid tissue development by interacting with both lymphoid tissue inducer and organizer cells, initiating early aggregation and supporting lymphotoxin-mediated signaling pathways essential for lymphoid structure maturation. Additionally, DCs release chemokines attracting and anchoring immune cells in lymphoid tissues and regulate the formation and the overall size of high endothelial venule system, which mediate immune cell trafficking into lymphoid tissues. The dynamic crosstalk between DCs and fibroblastic reticular cells (FRC), which facilitate immune cell interactions and compartmentalization, is essential for lymphoid tissue specialization and function, though the precise cellular and molecular mechanisms of DC/FRC crosstalk remain to be fully elucidated. Finally, studies in mice and humans suggest that DC subsets are pivotal in T follicular helper cell differentiation, essential for humoral immunity in B cell follicles of lymphoid tissues, therefore emphasizing DCs’ critical role also in supporting B cell maturation and antibody responses in the germinal centers of lymphoid organs.