Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

Charles Antoine Dutertre, Etienne Becht, Sergio Erdal Irac, Ahad Khalilnezhad, Vipin Narang, Shabnam Khalilnezhad, Pei Y. Ng, Lucas L. van den Hoogen, Jing Yao Leong, Bernett Lee, Marion Chevrier, Xiao Meng Zhang, Pearly Jean Ai Yong, Geraldine Koh, Josephine Lum, Shanshan Wu Howland, Esther Mok, Jinmiao Chen, Anis Larbi, Henry Kun Kiaang TanTony Kiat Hon Lim, Panagiota Karagianni, Athanasios G. Tzioufas, Benoit Malleret, Joshua Brody, Salvatore Albani, Joel van Roon, Timothy Radstake, Evan W. Newell, Florent Ginhoux

Research output: Contribution to journalArticlepeer-review

269 Scopus citations

Abstract

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. Using high-dimensional protein and RNA single-cell analyses, Dutertre et al. analyze human dendritic cell and monocyte subsets and identify markers that delineate them and unravel their heterogeneity. They also reveal the presence of inflammatory CD14+ DC3s, a subset of cDC2s, that correlate with disease progression and may be functionally involved in systemic lupus erythematosus immunopathology.

Original languageEnglish
Pages (from-to)573-589.e8
JournalImmunity
Volume51
Issue number3
DOIs
StatePublished - 17 Sep 2019

Keywords

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

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