Dendritic cell homeostasis in the splenic microenvironment.

The spleen is a central immune organ that surveys blood-borne pathogens and coordinates systemic immune responses. Within this organ, conventional dendritic cell (cDC) subsets occupy blood-exposed niches that enable efficient antigen capture and rapid initiation of T cell activation. While splenic cDC1s maintain relatively stable localization and functional programs, cDC2s represent a highly heterogeneous population whose positioning, retention, and survival are actively shaped by local microenvironmental cues. During systemic infection, extensive cross-talk between cDC subsets and other immune cells drives reciprocal sensing and niche remodeling, dynamically reorganizing splenic immune architecture to optimize antigen presentation and adaptive immunity. Loss of these pathways under chronic inflammation or aging disrupts the mechanical and molecular cues that stabilize cDCs at the blood-immune interface, leading to impaired antigen capture, altered T cell differentiation, and weakened responses to circulating pathogens. Targeting circulation-exposed splenic cDC niches may therefore offer new opportunities for improving systemic vaccination and immunomodulation.