Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches

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....

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Veröffentlicht in:	Science (American Association for the Advancement of Science) Jg. 363; H. 6432
Hauptverfasser:	Chakarov, Svetoslav, Lim, Hwee Ying, Tan, Leonard, Lim, Sheau Yng, See, Peter, Lum, Josephine, Zhang, Xiao-Meng, Foo, Shihui, Nakamizo, Satoshi, Duan, Kaibo, Kong, Wan Ting, Gentek, Rebecca, Balachander, Akhila, Carbajo, Daniel, Bleriot, Camille, Malleret, Benoit, Tam, John Kit Chung, Baig, Sonia, Shabeer, Muhammad, Toh, Sue-Anne Ee Shiow, Schlitzer, Andreas, Larbi, Anis, Marichal, Thomas, Malissen, Bernard, Chen, Jinmiao, Poidinger, Michael, Kabashima, Kenji, Bajenoff, Marc, Ng, Lai Guan, Angeli, Veronique, Ginhoux, Florent
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 15.03.2019
Schlagworte:	Animals Antigens, Ly Cell Lineage CX3C Chemokine Receptor 1 - genetics Dermis - immunology Disease Models, Animal Fibrosis Glycoproteins - analysis Histocompatibility Antigens Class II - genetics Lung - immunology Lung - pathology Macrophages - immunology Mice Mice, Inbred C57BL Monocytes - immunology Myocardium - immunology Organic Anion Transporters - genetics Sequence Analysis, RNA - methods Single-Cell Analysis - methods Transcriptome
ISSN:	1095-9203, 1095-9203
Online-Zugang:	Weitere Angaben
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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 MHCII CX3CR1 (Lyve1 MHCII ) and Lyve1 MHCII CX3CR1 (Lyve1 MHCII ) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localizations. Using a new mouse model of inducible macrophage depletion ( ), we found that the absence of Lyve1 MHCII IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs coexist across tissues and exhibit conserved niche-dependent functional programming.
AbstractList	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: Lyve1loMHCIIhiCX3CR1hi (Lyve1loMHCIIhi) and Lyve1hiMHCIIloCX3CR1lo (Lyve1hiMHCIIlo) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localizations. Using a new mouse model of inducible macrophage depletion (Slco2b1 flox/DTR), we found that the absence of Lyve1hiMHCIIlo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs coexist across tissues and exhibit conserved niche-dependent functional programming.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: Lyve1loMHCIIhiCX3CR1hi (Lyve1loMHCIIhi) and Lyve1hiMHCIIloCX3CR1lo (Lyve1hiMHCIIlo) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localizations. Using a new mouse model of inducible macrophage depletion (Slco2b1 flox/DTR), we found that the absence of Lyve1hiMHCIIlo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs coexist across tissues and exhibit conserved niche-dependent functional programming. 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 MHCII CX3CR1 (Lyve1 MHCII ) and Lyve1 MHCII CX3CR1 (Lyve1 MHCII ) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localizations. Using a new mouse model of inducible macrophage depletion ( ), we found that the absence of Lyve1 MHCII IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs coexist across tissues and exhibit conserved niche-dependent functional programming.
Author	Toh, Sue-Anne Ee Shiow Marichal, Thomas Angeli, Veronique Schlitzer, Andreas Malissen, Bernard Lim, Hwee Ying Balachander, Akhila Ng, Lai Guan See, Peter Nakamizo, Satoshi Bleriot, Camille Duan, Kaibo Shabeer, Muhammad Ginhoux, Florent Foo, Shihui Kabashima, Kenji Lum, Josephine Tam, John Kit Chung Baig, Sonia Zhang, Xiao-Meng Gentek, Rebecca Larbi, Anis Kong, Wan Ting Chakarov, Svetoslav Tan, Leonard Lim, Sheau Yng Malleret, Benoit Poidinger, Michael Bajenoff, Marc Chen, Jinmiao Carbajo, Daniel
Author_xml	– sequence: 1 givenname: Svetoslav orcidid: 0000-0002-0665-5417 surname: Chakarov fullname: Chakarov, Svetoslav organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 2 givenname: Hwee Ying orcidid: 0000-0003-3991-7855 surname: Lim fullname: Lim, Hwee Ying organization: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore – sequence: 3 givenname: Leonard orcidid: 0000-0002-6923-1021 surname: Tan fullname: Tan, Leonard organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 4 givenname: Sheau Yng orcidid: 0000-0002-5627-5017 surname: Lim fullname: Lim, Sheau Yng organization: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore – sequence: 5 givenname: Peter orcidid: 0000-0003-4428-7763 surname: See fullname: See, Peter organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 6 givenname: Josephine orcidid: 0000-0003-1108-5989 surname: Lum fullname: Lum, Josephine organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 7 givenname: Xiao-Meng surname: Zhang fullname: Zhang, Xiao-Meng organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 8 givenname: Shihui orcidid: 0000-0002-2908-8013 surname: Foo fullname: Foo, Shihui organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 9 givenname: Satoshi surname: Nakamizo fullname: Nakamizo, Satoshi organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 10 givenname: Kaibo surname: Duan fullname: Duan, Kaibo organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 11 givenname: Wan Ting surname: Kong fullname: Kong, Wan Ting organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 12 givenname: Rebecca orcidid: 0000-0001-6574-7242 surname: Gentek fullname: Gentek, Rebecca organization: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France – sequence: 13 givenname: Akhila surname: Balachander fullname: Balachander, Akhila organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 14 givenname: Daniel surname: Carbajo fullname: Carbajo, Daniel organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 15 givenname: Camille surname: Bleriot fullname: Bleriot, Camille organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 16 givenname: Benoit orcidid: 0000-0001-9658-7528 surname: Malleret fullname: Malleret, Benoit organization: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore – sequence: 17 givenname: John Kit Chung orcidid: 0000-0002-6269-3653 surname: Tam fullname: Tam, John Kit Chung organization: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore – sequence: 18 givenname: Sonia orcidid: 0000-0001-5195-3512 surname: Baig fullname: Baig, Sonia organization: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore, Singapore – sequence: 19 givenname: Muhammad surname: Shabeer fullname: Shabeer, Muhammad organization: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore, Singapore – sequence: 20 givenname: Sue-Anne Ee Shiow surname: Toh fullname: Toh, Sue-Anne Ee Shiow organization: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore, Singapore – sequence: 21 givenname: Andreas surname: Schlitzer fullname: Schlitzer, Andreas organization: Myeloid Cell Biology, Life & Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany – sequence: 22 givenname: Anis surname: Larbi fullname: Larbi, Anis organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 23 givenname: Thomas orcidid: 0000-0003-1688-6291 surname: Marichal fullname: Marichal, Thomas organization: WELBIO, Walloon Excellence in Life Sciences and Biotechnology, 1300 Wallonia, Belgium – sequence: 24 givenname: Bernard surname: Malissen fullname: Malissen, Bernard organization: Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS UMR, 13288 Marseille, France – sequence: 25 givenname: Jinmiao orcidid: 0000-0001-7547-6423 surname: Chen fullname: Chen, Jinmiao organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 26 givenname: Michael orcidid: 0000-0002-1047-2277 surname: Poidinger fullname: Poidinger, Michael organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 27 givenname: Kenji orcidid: 0000-0002-0773-0554 surname: Kabashima fullname: Kabashima, Kenji organization: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan – sequence: 28 givenname: Marc surname: Bajenoff fullname: Bajenoff, Marc organization: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France – sequence: 29 givenname: Lai Guan surname: Ng fullname: Ng, Lai Guan organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore – sequence: 30 givenname: Veronique orcidid: 0000-0002-2759-3497 surname: Angeli fullname: Angeli, Veronique organization: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore – sequence: 31 givenname: Florent orcidid: 0000-0002-2857-7755 surname: Ginhoux fullname: Ginhoux, Florent email: florent_ginhoux@immunol.a-star.edu.sg organization: Singapore Immunology Network (SIgN), ASTAR, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore. florent_ginhoux@immunol.a-star.edu.sg
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/30872492$$D View this record in MEDLINE/PubMed
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SubjectTerms	Animals Antigens, Ly Cell Lineage CX3C Chemokine Receptor 1 - genetics Dermis - immunology Disease Models, Animal Fibrosis Glycoproteins - analysis Histocompatibility Antigens Class II - genetics Lung - immunology Lung - pathology Macrophages - immunology Mice Mice, Inbred C57BL Monocytes - immunology Myocardium - immunology Organic Anion Transporters - genetics Sequence Analysis, RNA - methods Single-Cell Analysis - methods Transcriptome
Title	Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches
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