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

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

Immunity

10.1016/j.immuni.2019.08.008

https://doi.org/10.1016/j.immuni.2019.08.008

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 Ai Yong Jean, Geraldine Koh, Josephine Lum, Shanshan Howland Wu, Esther Mok, Jinmiao Chen, Anis Larbi, Henry Kun Kiaang Tan, Tony Kiat Hon Lim, Panagiota Karagianni, Athanasios G. Tzioufas, Benoit Malleret, Joshua Brody, Salvatore Albani, Joel van Roon, Timothy Radstake, Evan W. Newell, Florent Ginhoux

29 August 2019

Dutertre CA, Becht E, Irac SE, Khalilnezhad A, Narang V, Khalilnezhad S, Ng PY, van den Hoogen LL, Leong JY, Lee B, Chevrier M, Zhang XM, Yong PJA, Koh G, Lum J, Howland SW, Mok E, Chen J, Larbi A, Tan HKK, Lim TKH, Karagianni P, Tzioufas AG, Malleret B, Brody J, Albani S, van Roon J, Radstake T, Newell EW, Ginhoux F. Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells. Immunity. 2019 Sep 17;51(3):573-589.e8. doi: 10.1016/j.immuni.2019.08.008. Epub 2019 Aug 29. PMID: 31474513.

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 CD5−CD163+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.

This research is supported by the National Research Foundation, under its NRF-NRFI2017-02 project.

This paper is available at: https://doi.org/10.1016/j.immuni.2019.08.008

https://oar.a-star.edu.sg/communities-collections/articles/16842

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Singapore Immunology Network