1. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches.
- Author
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Chakarov S, Lim HY, Tan L, Lim SY, See P, Lum J, Zhang XM, Foo S, Nakamizo S, Duan K, Kong WT, Gentek R, Balachander A, Carbajo D, Bleriot C, Malleret B, Tam JKC, Baig S, Shabeer M, Toh SES, Schlitzer A, Larbi A, Marichal T, Malissen B, Chen J, Poidinger M, Kabashima K, Bajenoff M, Ng LG, Angeli V, and Ginhoux F
- Subjects
- Animals, Antigens, Ly, CX3C Chemokine Receptor 1 genetics, Cell Lineage, Dermis immunology, Disease Models, Animal, Fibrosis, Glycoproteins analysis, Histocompatibility Antigens Class II genetics, Membrane Transport Proteins, Mice, Mice, Inbred C57BL, Monocytes immunology, Myocardium immunology, Organic Anion Transporters genetics, Sequence Analysis, RNA methods, Single-Cell Analysis methods, Transcriptome, Lung immunology, Lung pathology, Macrophages immunology
- Abstract
Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation, and various pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within the tissue parenchyma remain poorly defined. Here we studied IMs from murine lung, fat, heart, and dermis. We identified two independent IM subpopulations that are conserved across tissues: Lyve1
lo MHCIIhi CX3CR1hi (Lyve1lo MHCIIhi ) and Lyve1hi MHCIIlo CX3CR1lo (Lyve1hi MHCIIlo ) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localizations. Using a new mouse model of inducible macrophage depletion ( Slco2b1flox/DTR ), we found that the absence of Lyve1hi MHCIIlo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs coexist across tissues and exhibit conserved niche-dependent functional programming., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)- Published
- 2019
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