Dendritic Cell Development

Dendritic cells (DCs) are a heterogeneous population of immune cells that are critical mediators of innate and adaptive immunity. DC precursors develop in the bone marrow. While plasmacytoid DCs complete development in the bone marrow, most DCs complete development in lymphoid and peripheral tissues. Knockout mouse models have identified several cytokines and transcription factors that are critical for DC development in vivo. A limited number of cytokines and transcription factors, including Flt-3 Ligand, Ikaros, PU.1/Spi-1, and GFI-1, are essential during early DC development and their silencing results in global reductions in DC numbers. Additional cytokines and transcriptional regulators are necessary during the late phases of DC differentiation. Late developmental factors act to promote or maintain the differentiation of specific DC subsets and include BATF3, ID2, E2-2, E4BP4, IRF2, IRF4, IRF8, RelB, Spi-B, STAT3, and STAT5. The final stage in DC development occurs upon activation. Activation of human and mouse DCs can be detected by upregulation of MHC class II, B7-1/CD80, B7-2/CD86, CD40/TNFRSF5, and CD83 expression. Understanding DC developmental pathways has facilitated the in vitro generation of DCs from bone marrow or blood-derived DC precursors using cytokine cocktails of Flt-3 Ligand, M-CSF, GM-CSF, and IL-4.