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Plasmacytoid Dendritic Cells

Plasmacytoid dendritic cells (pDCs) are a rare subset of dendritic cells that are morphologically and functionally unique from conventional dendritic cells (cDCs). pDC development requires Flt-3 Ligand and the transcription factor E2-2. Additional transcription factors required for pDC development include GFI-1, Ikaros, IRF7, IRF8, PU.1/Spi-1, and Spi-B. pDCs fully mature in the bone marrow prior to entering the bloodstream. In the inactive state, pDCs express low levels of MHC class II and have a spherical, secretory morphology similar to plasma cell lymphocytes. Upon activation, pDCs initially function in an innate capacity and secrete pro-inflammatory and anti-viral cytokines such as type I Interferons (IFNs), TNF-alpha, IL-6, and IL-12. In addition, they upregulate T cell co-stimulatory molecules, increase MHC class II expression, and develop a cDC-like morphology, enabling them to function as antigen-presenting cells. Human and mouse pDCs appear to develop and function similarly and express shared markers such as Integrin alpha X/CD11c, IRF7, IRF8, Spi-B, TLR7, and TLR9. In addition to these shared markers, they also express species-specific markers including CD303/CLEC4C/BDCA-2, Neuropilin-1/BDCA-4, and IL-3 R alpha/CD123 on human pDCs and BST2/Tetherin, Siglec-H, and Ly-6C on mouse pDCs.