Bridging pDCs and cDCs: The Identity of Transitional Dendritic Cells

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.