Subsets of CD1c⁺ DCs: Dendritic Cell Versus Monocyte Lineage

Currently three bona fide dendritic cell (DC) types are distinguished in human blood. Herein we focus on type 2 DCs (DC2s) and compare the three defining markers CD1c, CD172, and CD301. When using CD1c to define DC2s, a CD14⁺ and a CD14^- subset can be detected. The CD14⁺ subset shares features with monocytes, and this includes substantially higher expression levels for CD64, CD115, CD163, and S100A8/9. We review the current knowledge of these CD1c⁺CD14⁺ cells as compared to the CD1c⁺CD14^- cells with respect to phenotype, function, transcriptomics, and ontogeny. Here, we discuss informative mutations, which suggest that two populations have different developmental requirements. In addition, we cover subsets of CD11c⁺CD8^- DC2s in the mouse, where CLEC12A⁺ESAM^low cells, as compared to the CLEC12A^-ESAM^high subset, also express higher levels of monocyte-associated markers CD14, CD3, and CD115. Finally, we summarize, for both man and mouse, the data on lower antigen presentation and higher cytokine production in the monocyte-marker expressing DC2 subset, which demonstrate that the DC2 subsets are also functionally distinct.