Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells
Dutertre, Charles Antoine; Becht, Etienne; Irac, Sergio Erdal; Khalilnezhad, Ahad; Narang, Vipin; Khalilnezhad, Shabnam; Ng, Pei Y.; van den Hoogen, Lucas L.; Leong, Jing Yao; Lee, Bernett; Chevrier, Marion; Zhang, Xiao Meng; Yong, Pearly Jean Ai; Koh, Geraldine; Lum, Josephine; Howland, Shanshan Wu; Mok, Esther; Chen, Jinmiao; Larbi, Anis; Tan, Henry Kun Kiaang; Lim, Tony Kiat Hon; Karagianni, Panagiota; Tzioufas, Athanasios G.; Malleret, Benoit; Brody, Joshua; Albani, Salvatore; van Roon, Joel; Radstake, Timothy; Newell, Evan W.; Ginhoux, Florent
(2019) Immunity, volume 51, issue 3, pp. 573 - 589.e8
(Article)
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
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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. 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.
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Keywords: CD88, CD89, DC2, DC3, dendritic cell, FcεRIα, inflammatory DC, lupus, monocyte, pre-DC, SLE, Immunology and Allergy, Immunology, Infectious Diseases
ISSN: 1074-7613
Publisher: Cell Press
Note: Funding Information: We thank L. Robinson of Insight Editing London for critical review and editing of the manuscript and M.L. Ng, S.H. Tan, and T.B. Lu from the Electron Microscope Unit of NUS for their assistance. F.G. is an EMBO YIP awardee and is supported by Singapore Immunology Network (SIgN) core funding, as well as a Singapore National Research Foundation Senior Investigatorship (NRFI) NRF2016NRF-NRFI001-02 . The CyTOF, bioinformatics, and immunogenomics platforms are part of the SIgN Immunomonitoring platform (supported by a BMRC IAF 311006 grant and BMRC transition funds # H16/99/b0/011 ). Funding Information: We thank L. Robinson of Insight Editing London for critical review and editing of the manuscript and M.L. Ng, S.H. Tan, and T.B. Lu from the Electron Microscope Unit of NUS for their assistance. F.G. is an EMBO YIP awardee and is supported by Singapore Immunology Network (SIgN) core funding, as well as a Singapore National Research Foundation Senior Investigatorship (NRFI) NRF2016NRF-NRFI001-02. The CyTOF, bioinformatics, and immunogenomics platforms are part of the SIgN Immunomonitoring platform (supported by a BMRC IAF 311006 grant and BMRC transition funds #H16/99/b0/011). Experiments, C.-A.D. S.E.I. A.K. S.K. P.Y.N. P.J.A.Y. G.K. J.L. E.M. and B.M.; Data Analysis, C.-A.D. E.B. A.K. V.N. B.L. M.C. X.M.Z. J.C. and B.M.; Spleen and Tonsil Samples, H.K.K.T. and T.K.H.L.; SLE Samples, L.v.d.H, J.Y.L. P.K. A.G.T. S.A. J.v.R. and T.R.; FLT3L-Injected Patients? Samples. J.B.; Writing of the Manuscript, C.-A.D. and F.G.; Intellectual Input, S.W.H, A.L. and E.W.N.; Project Supervision, C.-A.D. and F.G.; Study Conceptualization, C.-A.D. and F.G. C.-A.D. and F.G. are co-inventors of a patent: Singapore Patent Application Number: 10201905956V. Publisher Copyright: © 2019 Elsevier Inc.
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