Various subsets of dendritic cells (DCs) and monocytes exist that have overlapping phenotypes and functions, but delineating these subsets without ambiguity is a challenge. In a new study aimed at distinguishing monocytes from type 2 conventional DCs (cDC2s), researchers have identified a subset of cDC2s that is expanded in the blood of patients with systemic lupus erythematosus (SLE) and could be functionally involved in SLE immunopathology.
“We created a pipeline named InfinityFlow that, through machine learning-based methods, enabled us to generate high-dimensional protein expression data at the single cell level”, explains Evan Newell, an author on the study. “Integrating these data allowed us to clarify grey zones in the definition of human blood mononuclear myeloid cell subsets (DCs and monocytes)”.
The researchers identified markers that could distinguish monocytes (CD88 and CD89) from cDC2s (HLA-DQ and FcεRIα) and further subdivide cDC2s into four phenotypically and functionally distinct subsets (on the basis of the expression of CD5, CD163 and CD14). One of the subsets, CD5−CD163+CD14+ cells (also referred to as inflammatory CD14+ DC3s), was increased in the blood of patients with SLE compared with the blood of patients with systemic sclerosis or healthy individuals.
Importantly, the proportion of circulating CD163+ DC3s (consisting of the aforementioned CD5−CD163+CD14+ cells and CD5−CD163+CD14−cells) correlated with disease activity in these patients. Furthermore, RNA-sequencing analysis found that many interferon-stimulated genes, including genes encoding inflammatory cytokines, were upregulated in circulating CD163+ DC3s from patients with SLE.
the proportion of circulating CD163+ DC3s … correlated with disease activity
Unravelling the heterogeneity of DC subpopulations could help in the development of therapies for diseases such as SLE. “We next aim to target (eliminate or modulate) CD14+ DC3s in SLE and several other inflammatory and autoimmune diseases,” says corresponding author Florent Ginhoux.
References
Original article
Dutertre, C.-A. et al. Single-cell analysis of human mononuclear phagocytes reveals subset-defining markers and identifies circulating inflammatory dendritic cells. Immunity 51, 573–589.e8 (2019)
Related article
Cheung, P. et al. Single-cell technologies — studying rheumatic diseases one cell at a time. Nat. Rev. Rheum. 15, 340–354 (2019)
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McHugh, J. Newly defined pro-inflammatory DC subset expanded in SLE. Nat Rev Rheumatol 15, 637 (2019). https://doi.org/10.1038/s41584-019-0311-x
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DOI: https://doi.org/10.1038/s41584-019-0311-x