Identity, Functions, and the Spatiotemporal Maturation of Type 1 Conventional Dendritic Cells

ABSTRACT Dendritic cells (DCs) are essential regulators of adaptive immunity, functioning as professional antigen‐presenting cells that bridge innate sensing with the induction of adaptive immunity and immune memory. The DC population is heterogeneous, encompassing numerous phenotypic subsets depending on the tissue, pathophysiological condition and species studied, which historically complicated their classification. Advances in bulk or single‐cell transcriptomics and ontogenetic studies have clarified DC heterogeneity and highlighted type 1 conventional DCs (cDC1s) for their unique ability to induce protective CD8 + T cell responses against cancer and intracellular pathogens. Beyond immunity, DCs also maintain tolerance to self and harmless antigens. Contrary to earlier assumptions that tolerogenic DCs are simply immature, recent evidence shows that both immunogenic and tolerogenic maturation involve an extensive and convergent reprogramming of cDC1s during the activation process licensing them for shaping T cell responses, a process referred to as DC maturation. This evolving understanding is reshaping how we study DCs, including the necessity to integrate the timing of DC maturation and their microanatomical redistribution during this process. The novel insights these studies are bringing carry significant implications for vaccines or immunotherapies against intracellular pathogens or cancers, and treatments against allergy or autoimmunity.