Juliana Idoyaga, Hai Ni, Raul A. Maqueda‐Alfaro
ABSTRACT Transitional dendritic cells (tDCs) have emerged as a compelling addition to the dendritic cell (DC) network—a hybrid subset that bridges plasmacytoid (pDC) and conventional (cDC) lineages, particularly conventional type 2 DCs (cDC2s). First identified through high‐dimensional single‐cell profiling, tDCs combine features of both pDCs and cDC2s yet follow a distinct developmental trajectory with unique effector functions. Although ontogenetically related to pDCs, tDCs do not produce type I interferon but instead mount a robust IL‐1β response upon pathogen sensing, positioning them as rapid initiators of innate inflammation. tDCs also mirror cDC2s in their ability to capture antigen and prime naïve CD4 + T cells. Importantly, tDCs exist in progressive states—tDC lo , tDC hi , CD11b − tDC2s and tDC‐derived DC2s (tDC2s)—reflecting a unidirectional differentiation continuum. Recognizing this dynamic spectrum is essential for properly interpreting tDC function and avoiding fragmented nomenclature. In this review, we synthesize current insights into tDC biology across species—tracing their origin, phenotypic and transcriptional trajectory, tissue localization, and immune function. Although tDCs challenge the rigid pDC/cDC dichotomy, they exemplify a broader principle: DC identity is not fixed but temporally programmed, even during homeostasis. Embracing this plasticity may unlock new opportunities for therapeutic intervention in infection, cancer, and autoimmunity.