Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease.

Abstract

Mononuclear phagocytes (MNPs) encompass dendritic cells, monocytes, and macrophages (MoMac), which exhibit antimicrobial, homeostatic, and immunoregulatory functions. We integrated 178,651 MNPs from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and define conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialized cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumor-associated macrophage populations. In particular, we focused on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated in the tumor periphery in a T cell-dependent manner via interferon-γ (IFN-γ) and CD40/CD40L-induced maturation from IFN-primed monocytes. IL4I1_Macs exhibited immunosuppressive characteristics through tryptophan degradation and promoted the entry of regulatory T cell into tumors. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.

• Authors: Kevin Mulder, Amit Ashok Patel, Wan Ting Kong, Cécile Piot, Evelyn Halitzki, Garett Dunsmore, Shabnam Khalilnezhad, Sergio Erdal Irac, Agathe Dubuisson, Marion Chevrier, Xiao Meng Zhang, John Kit Chung Tam, Tony Kiat Hon Lim, Regina Men Men Wong, Rhea Pai, Ahmed Ibrahim Samir Khalil, Pierce Kah Hoe Chow, Suny Z Wu, Ghamdan Al-Eryani, Daniel Roden, Alexander Swarbrick, Jerry Kok Yen Chan, Salvatore Albani, Lisa Derosa, Laurence Zitvogel, Ankur Sharma, Jinmiao Chen, Aymeric Silvin, Antonio Bertoletti, Camille Blériot, Charles-Antoine Dutertre, Florent Ginhoux
• Journal: Immunity (Immunity) Vol. 54 Issue 8 Pg. 1883-1900.e5 (08 10 2021) ISSN: 1097-4180 [Electronic] United States
• PMID: 34331874 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• IFNG protein, human
• RNA, Small Cytoplasmic
• Interferon-gamma
• IL4I1 protein, human
• L-Amino Acid Oxidase

Topics

• Arthritis, Rheumatoid (immunology)
• COVID-19 (immunology)
• Dendritic Cells (immunology)
• Gene Expression (genetics, immunology)
• Gene Expression Profiling
• Humans
• Interferon-gamma (immunology)
• L-Amino Acid Oxidase (metabolism)
• Liver Cirrhosis (immunology)
• Macrophages (immunology)
• Monocytes (immunology)
• Neoplasms (immunology)
• RNA, Small Cytoplasmic (genetics)
• Single-Cell Analysis
• T-Lymphocytes, Regulatory (immunology)
• Transcriptome (genetics, immunology)
• Tumor-Associated Macrophages (immunology)