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 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
Author Information
Charles-Antoine Dutertre: Singapore Immunology Network, A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore; Program in Emerging Infectious Disease, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
Sergio Erdal Irac: Singapore Immunology Network, A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore; Program in Emerging Infectious Disease, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
Ahad Khalilnezhad: Singapore Immunology Network, A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.
Pei Y Ng: Singapore Immunology Network, A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore.
Lucas L van den Hoogen: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands; Laboratory of Translational Immunology, Department of Immunology, University Medical, Center Utrecht, 3584 CX Utrecht, the Netherlands.
Jing Yao Leong: Translational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, the Academia, 20 College Road, Discovery Tower Level 8, Singapore 169856, Singapore.
Pearly Jean Ai Yong: Singapore Health Services Flow Cytometry Core Platform, 20 College Road, The Academia, Discovery Tower Level 10, Singapore 169856, Singapore.
Henry Kun Kiaang Tan: KK Research Centre, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore.
Tony Kiat Hon Lim: Department of Pathology, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore.
Panagiota Karagianni: Department of Pathophysiology, School of Medicine, University of Athens, 75 M. Asias Street, Athens 11527, Greece.
Athanasios G Tzioufas: Department of Pathophysiology, School of Medicine, University of Athens, 75 M. Asias Street, Athens 11527, Greece.
Benoit Malleret: Singapore Immunology Network, A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.
Joshua Brody: Icahn School of Medicine at Mount Sinai, Hess Center for Science and Medicine, New York 10029, USA.
Salvatore Albani: Translational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, the Academia, 20 College Road, Discovery Tower Level 8, Singapore 169856, Singapore.
Joel van Roon: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands; Laboratory of Translational Immunology, Department of Immunology, University Medical, Center Utrecht, 3584 CX Utrecht, the Netherlands.
Timothy Radstake: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands; Laboratory of Translational Immunology, Department of Immunology, University Medical, Center Utrecht, 3584 CX Utrecht, the Netherlands.
Evan W Newell: Singapore Immunology Network, A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore.
Florent Ginhoux: Singapore Immunology Network, A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore; Translational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, the Academia, 20 College Road, Discovery Tower Level 8, Singapore 169856, Singapore. Electronic address: florent_ginhoux@immunol.a-star.edu.sg.
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 CD5CD163CD14 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.
