Dendritic Cells

Dendritic cells (DCs) are key mediators of the innate and adaptive immune responses due to their abilities to: 1) upregulate MHC molecules and costimulatory receptors upon pathogen recognition, 2) capture, process, and present antigens to naïve T cells, and 3) produce polarizing cytokines that promote pathogen-specific effector T cell differentiation and activation. In addition, DCs can promote self-tolerance by secreting tolerogenic cytokines that induce the differentiation of regulatory T cells. As a result of their capacity to regulate T cell responses, there is considerable interest in DCs as potential therapeutic targets. With the exception of Langerhans cells which develop from precursor cells in the yolk sac and fetal liver, mouse dendritic cells develop from macrophage-dendritic cell precursors (MDPs) in the bone marrow. MDPs give rise to common monocyte progenitors (cMoPs) and common DC progenitors (CDPs). The CDPs subsequently give rise to plasmacytoid dendritic cells (pDCs) and pre-DCs (cDC progenitors), which migrate through the blood to lymphoid and non-lymphoid tissues where they differentiate into classical DC (cDC) subsets. In contrast to cDCs, monocyte-derived dendritic cells (MoDCs) arise from cMoPs that give rise to blood monocytes, which migrate to inflamed tissues, where they differentiate into MoDCs. In humans, both granulocyte-macrophage progenitors (GMPs) and multi-lymphoid progenitors (MLPs) have been suggested to have the potential to differentiate into a MDP- or CDP-like progenitor. These progenitors are subsequently thought to differentiate into DCs through pathways similar to what has been described in mouse.