Dendritic Cell Organization and Function in Innate and Adaptive Immune Defense Within Lymph Nodes

Lymph nodes (LNs) are highly organized secondary lymphoid organs that serve as critical hubs for immune defense. They filter lymph and enable efficient immune surveillance, elicit potent innate responses to prevent systemic pathogen spread, and generate adaptive immunity for long-lived protection. It has now been established that conventional dendritic cells (DCs), canonically recognized as professional antigen-presenting cells that instruct T cell responses, play foundational roles in coordinating all these functions of the LN. DCs are the most abundant innate cell type in the LN parenchyma, and their ability to mediate these processes is intimately tied to their spatial organization. Rather than being randomly dispersed, different DC subsets preferentially occupy distinct niches within the tissue. This positioning regulates their homeostatic maintenance, access to different types of antigens, and interactions with other immune cells, which collectively shape the ensuing immune response. In this review, we summarize the current understanding of how the spatiotemporal dynamics and functional cooperation of DC subsets, and other innate populations, underpin diverse immunological functions of the LN, ranging from steady-state surveillance to the development of synchronized and tailored innate and adaptive responses to pathogens or following vaccination.