Immunity
Volume 51, Issue 3, 17 September 2019, Pages 573-589.e8
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Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

https://doi.org/10.1016/j.immuni.2019.08.008Get rights and content
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Highlights

  • InfinityFlow protein expression analysis reveals DC- and monocyte-specific markers

  • Monocytes are CD88+CD89+, while cDC2s are HLA-DQ+FcεRIα+

  • cDC2s comprise CD5+ DC2s and CD5CD163+/−CD14+/− DC3s

  • Pro-inflammatory CD14+ DC3 expansion correlates with disease activity in SLE patients

Summary

Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DCs) and monocytes, but the extent of their heterogeneity and distinct markers for subset identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we identified distinct markers to delineate monocytes from conventional DC2 (cDC2s). Using CD88 and CD89 for monocytes and HLA-DQ and FcεRIα for cDC2s allowed for their specific identification in blood and tissues. We also showed that cDC2s could be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163, and CD14 expression, including a distinct subset of circulating inflammatory CD5CD163+CD14+ cells related to previously defined DC3s. These inflammatory DC3s were expanded in systemic lupus erythematosus patients and correlated with disease activity. These findings further unravel the heterogeneity of DC subpopulations in health and disease and may pave the way for the identification of specific DC subset-targeting therapies.

Keywords

monocyte
dendritic cell
pre-DC
DC2
DC3
inflammatory DC
CD88
CD89
FcεRIα
SLE
lupus

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