Subsets of CD1c+ DCs: Dendritic Cell Versus Monocyte Lineage
Lukas Heger1, Thomas P Hofer2, Venetia Bigley3
1Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander University of Erlangen-Nürnberg (FAU), University Hospital Erlangen, Erlangen, Germany.
Insights
Type 2 dendritic cells (DC2s) in human blood include CD1c+CD14+ and CD1c+CD14- subsets. These DC2 subsets exhibit distinct phenotypes, developmental needs, and functions, with CD1c+CD14+ cells showing monocyte-like characteristics.
Area of Science:
- Immunology
- Cell Biology
Background:
- Three bona fide dendritic cell (DC) types are recognized in human blood.
- Type 2 DCs (DC2s) are a key focus, defined by markers like CD1c, CD172, and CD301.
- CD1c+ DC2s can be further divided into CD14+ and CD14- subsets.
Purpose of the Study:
- To compare the CD1c+CD14+ and CD1c+CD14- DC2 subsets in humans.
- To investigate the phenotypic, functional, transcriptomic, and ontogenic differences between these subsets.
- To explore analogous DC2 subsets in mice and their functional distinctions.
Main Methods:
- Comparative analysis of DC2 subsets based on cell surface marker expression (CD1c, CD14, CD64, CD115, CD163, S100A8/9).
- Review of existing knowledge on phenotype, function, transcriptomics, and ontogeny.
- Examination of informative mutations and mouse DC2 subsets (CLEC12A, ESAM).
Main Results:
- The CD1c+CD14+ DC2 subset expresses higher levels of monocyte-associated markers (CD64, CD115, CD163, S100A8/9) compared to the CD1c+CD14- subset.
- Informative mutations suggest different developmental requirements for the two human DC2 subsets.
- Mouse DC2 subsets (CLEC12A+ESAMlow) also show higher monocyte marker expression (CD14, CD3, CD115).
Conclusions:
- Human and mouse DC2 subsets expressing monocyte markers are functionally distinct.
- These subsets exhibit lower antigen presentation and higher cytokine production.
- The findings highlight functional divergence within DC2 populations based on monocyte marker expression.
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+ESAMlow cells, as compared to the CLEC12A-ESAMhigh 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.
