Inflammatory/Monocyte-derived Dendritic Cells

Monocytes can differentiate into dendritic cells (DCs) at sites of inflammation. Multiple subsets of inflammatory/monocyte-derived DCs (moDCs) have been experimentally characterized in mice in vivo. They arise from Ly-6C⁺ monocytes in the presence of GM-CSF following CCR6-dependent migration to sites of inflammation. They may also be recruited to the skin in a CCR2-dependent manner to replenish depleted epidermal Langerhans cell populations. Mouse moDCs have been shown to mediate antigen-specific T cell activation and promote a Th1 immune response via IL-12 production. They can be identified by MHC class II and Ly-6C expression, and may also express Integrin alpha M/CD11b, Integrin alpha X/CD11c, DC-SIGN/CD209, and MAC-3. A specific TNF-alpha and iNOS-producing subset of mouse MoDCs (TipDCs) has been characterized that is recruited to the spleen upon Listeria infection. In humans, TNF-alpha-secreting pro-inflammatory DCs identified in human peripheral blood are thought to correspond to mouse moDCs. Human moDCs have been shown to be generated in vitro from CD14⁺ monocytes cultured in the presence of GM-CSF and IL-4. In vitro-generated human moDCs express MHC class II/HLA-DR, Integrin alpha X/CD11c, and Fc gamma RIII/CD16, and lose CD14 expression upon differentiation.