pDCs

Plasmacytoid dendritic cells, usually abbreviated pDCs, are a specialized subset of dendritic cells characterized by their ability to produce large amounts of type I interferons in response to viral infections. They arise from bone marrow precursors and depend on Flt3 ligand for development; in humans they circulate in peripheral blood at low frequency and populate lymphoid and non-lymphoid tissues.

Phenotypically, human pDCs are typically CD4 positive and express the high-affinity IL-3 receptor CD123, along with surface markers BDCA-2 (CD303) and BDCA-4 (CD304). They are generally lineage negative (lacking markers of myeloid and lymphoid lineages) and express Toll-like receptors TLR7 and TLR9, enabling detection of viral RNA and unmethylated CpG DNA.

Functionally, pDCs are among the most potent producers of type I interferons, especially IFN-α, following sensing of viral nucleic acids through TLR7/9. The interferon response establishes an antiviral state and shapes the ensuing adaptive immune response. In addition to cytokine production, pDCs can present antigen and provide co-stimulatory signals, though their antigen-presenting capacity is typically weaker than that of conventional dendritic cells.

Clinical and therapeutic relevance: pDCs contribute to the pathogenesis of autoimmune diseases such as systemic lupus erythematosus, where sustained IFN-α signaling is implicated. They are also explored as targets in therapies aimed at modulating the type I interferon pathway, as well as as components of vaccine strategies and immunotherapies for infections and cancer. Research continues to define their precise roles in different contexts and tissues.