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Mulder, Kevin; Patel, Amit Ashok; Kong, Wan Ting; Piot, Cécile; Halitzki, Evelyn; Dunsmore, Garett; Khalilnezhad, Shabnam; Irac, Sergio Erdal; Dubuisson, Agathe; Chevrier, Marion; Zhang, Xiao Meng; Tam, John Kit Chung; Lim, Tony Kiat Hon; Wong, Regina Men Men; Pai, Rhea; Khalil, Ahmed Ibrahim Samir; Chow, Pierce Kah Hoe; Wu, Suny Z.; Al-Eryani, Ghamdan; Roden, Daniel; Swarbrick, Alexander; Chan, Jerry Kok Yen; Albani, Salvatore; Derosa, Lisa; Zitvogel, Laurence; Sharma, Ankur; Chen, Jinmiao; Silvin, Aymeric; Bertoletti, Antonio; Blériot, Camille; Dutertre, Charles-Antoine; Ginhoux, Florent
Immunity (Cambridge, Mass.), 08/2021, Letnik: 54, Številka: 8Journal Article
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. Display omitted •Cross-tissue integration of scRNA from monocytes and macrophages in health and disease•Conserved gene signatures of mononuclear phagocyte populations in human tissues•IL4I1+PD-L1+IDO1+ and TREM2+ TAM subsets accumulate in human tumors•IL4I1+PD-L1+IDO1+ TAM in the tumor periphery exhibit immunosuppressive characteristics Mulder et al. integrate 178,651 human mononuclear phagocytes (MNPs) from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE) that enables the definition of conserved gene signatures of MNP populations. This integrated approach provides a robust, online-available platform (https://gustaveroussy.github.io/FG-Lab/) for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.
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