1. Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease.
- Author
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Mulder K, Patel AA, Kong WT, Piot C, Halitzki E, Dunsmore G, Khalilnezhad S, Irac SE, Dubuisson A, Chevrier M, Zhang XM, Tam JKC, Lim TKH, Wong RMM, Pai R, Khalil AIS, Chow PKH, Wu SZ, Al-Eryani G, Roden D, Swarbrick A, Chan JKY, Albani S, Derosa L, Zitvogel L, Sharma A, Chen J, Silvin A, Bertoletti A, Blériot C, Dutertre CA, and Ginhoux F
- Subjects
- Arthritis, Rheumatoid immunology, COVID-19 immunology, Gene Expression genetics, Gene Expression Profiling, Humans, Interferon-gamma immunology, L-Amino Acid Oxidase metabolism, Liver Cirrhosis immunology, Macrophages immunology, Neoplasms immunology, RNA, Small Cytoplasmic genetics, Single-Cell Analysis, T-Lymphocytes, Regulatory immunology, Transcriptome immunology, Dendritic Cells immunology, Gene Expression immunology, Monocytes immunology, Transcriptome genetics, Tumor-Associated Macrophages immunology
- 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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