Subsets of CD1c+ DCs: Dendritic Cell Versus Monocyte Lineage

Abstract

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.

Keywords: CD14; CD172; CD1c; CD301; DC subsets; DC2; dendritic cells.

Figure 1

Illustration of CD1c⁺ DCs and its subsets in human blood. Whole blood was stained with CD14, CD16, CD19, HLA-DR, and CD1c antibodies and the expression of CD1c (A) compared to isotype control (B) was analyzed on HLA-DR⁺ non-B cells. Of note, the CD14^low CD1c⁻ cells in (A) represent the CD16⁺ monocytes. (C, D) show additional staining for CD5. In the example in (C), the CD1c⁺ cells are divided into a CD14⁺ subset (green) and a CD14⁻ subset (blue). As shown in (D), the CD14⁻ subset in blue can be further subdivided into CD5⁺ and CD5⁻ cells. In the lower left there is a population of CD14⁻ CD5⁻ cells. Red arrows indicate the gating sequence.

Figure 2

Characterization of subsets of human DC2s in the recent literature. The different studies are listed at the top, the upper panel gives the subsets with pure DC features, the lower panel shows the subsets with monocyte features. Characteristic transcription factors, cell surface markers and functional properties are given when available. The cellular images are provided and adapted from Servier Medical Art (smart.servier.com).

Figure 3

Properties of two main DC2 subsets in man and mouse. The markers are listed based on a higher expression in the respective subset compared to the other subset, i.e. the other subset can also be positive but at a lower level. This cartoon is restricted to the subset with monocyte features as compared to a subset covering the remaining DC2 cells. The latter has been reported to include up to three distinct populations as detailed in the text. lin⁻ = lineage negative. The human data are a summary of a series of studies compiled in Figure 2 . The mouse data refer to Lewis et al., 2011, and Kasahara et al., 2012. The cellular images are provided and adapted from Servier Medical Art (smart.servier.com).