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

Svetoslav Chakarov; Hwee Ying Lim; Leonard Tan; Sheau Yng Lim; Peter See; Josephine Lum; Xiao-Meng Zhang; Shihui Foo; Satoshi Nakamizo; Kaibo Duan; Wan Ting Kong; Rebecca Gentek; Akhila Balachander; Daniel Carbajo; Camille Bleriot; Benoit Malleret; John Kit Chung Tam; Sonia Baig; Muhammad Shabeer; Sue-Anne Ee Shiow Toh; Andreas Schlitzer; Anis Larbi; Thomas Marichal; Bernard Malissen; Jinmiao Chen; Michael Poidinger; Kenji Kabashima; Marc Bajenoff; Lai Guan Ng; Veronique Angeli; Florent Ginhoux

doi:10.1126/science.aau0964

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

Svetoslav Chakarov, Hwee Ying Lim, Leonard Tan, Sheau Yng Lim, Peter See, Josephine Lum, Xiao-Meng Zhang, Shihui Foo, Satoshi Nakamizo, Kaibo Duan, Wan Ting Kong, Rebecca Gentek, Akhila Balachander, Daniel Carbajo, Camille Bleriot, Benoit Malleret, John Kit Chung Tam, Sonia Baig, Muhammad Shabeer, Sue-Anne Ee Shiow TohAndreas Schlitzer, Anis Larbi, Thomas Marichal, Bernard Malissen, Jinmiao Chen, Michael Poidinger, Kenji Kabashima, Marc Bajenoff, Lai Guan Ng, Veronique Angeli, Florent Ginhoux

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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^loMHCII^hiCX3CR1^hi (Lyve1^loMHCII^hi) and Lyve1^hiMHCII^loCX3CR1^lo (Lyve1^hiMHCII^lo) 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 Lyve1^hiMHCII^lo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs coexist across tissues and exhibit conserved niche-dependent functional programming.

Original language	English
Article number	eaau0964
Journal	Science
Volume	363
Issue number	6432
DOIs	https://doi.org/10.1126/science.aau0964
Publication status	Published - 15 Mar 2019

Keywords / Materials (for Non-textual outputs)

Animals
Antigens, Ly
CX3C Chemokine Receptor 1/genetics
Cell Lineage
Dermis/immunology
Disease Models, Animal
Fibrosis
Glycoproteins/analysis
Histocompatibility Antigens Class II/genetics
Lung/immunology
Macrophages/immunology
Membrane Transport Proteins
Mice
Mice, Inbred C57BL
Monocytes/immunology
Myocardium/immunology
Organic Anion Transporters/genetics
Sequence Analysis, RNA/methods
Single-Cell Analysis/methods
Transcriptome

Access to Document

10.1126/science.aau0964

Rebecca Gentek
- Deanery of Clinical Sciences - Chancellors Research Fellow (PI)
- Centre for Inflammation Research
Person: Academic: Research Active

Cite this

Chakarov, S., Lim, H. Y., Tan, L., Lim, S. Y., See, P., Lum, J., Zhang, X.-M., Foo, S., Nakamizo, S., Duan, K., Kong, W. T., Gentek, R., Balachander, A., Carbajo, D., Bleriot, C., Malleret, B., Tam, J. K. C., Baig, S., Shabeer, M., ... Ginhoux, F. (2019). Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches. Science, 363(6432), Article eaau0964. https://doi.org/10.1126/science.aau0964

@article{5176330dbac149c6ac7c7241d646c0e3,

title = "Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches",

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: 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 (Slco2b1flox/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.",

keywords = "Animals, Antigens, Ly, CX3C Chemokine Receptor 1/genetics, Cell Lineage, Dermis/immunology, Disease Models, Animal, Fibrosis, Glycoproteins/analysis, Histocompatibility Antigens Class II/genetics, Lung/immunology, Macrophages/immunology, Membrane Transport Proteins, Mice, Mice, Inbred C57BL, Monocytes/immunology, Myocardium/immunology, Organic Anion Transporters/genetics, Sequence Analysis, RNA/methods, Single-Cell Analysis/methods, Transcriptome",

author = "Svetoslav Chakarov and Lim, {Hwee Ying} and Leonard Tan and Lim, {Sheau Yng} and Peter See and Josephine Lum and Xiao-Meng Zhang and Shihui Foo and Satoshi Nakamizo and Kaibo Duan and Kong, {Wan Ting} and Rebecca Gentek and Akhila Balachander and Daniel Carbajo and Camille Bleriot and Benoit Malleret and Tam, {John Kit Chung} and Sonia Baig and Muhammad Shabeer and Toh, {Sue-Anne Ee Shiow} and Andreas Schlitzer and Anis Larbi and Thomas Marichal and Bernard Malissen and Jinmiao Chen and Michael Poidinger and Kenji Kabashima and Marc Bajenoff and Ng, {Lai Guan} and Veronique Angeli and Florent Ginhoux",

note = "Copyright {\textcopyright} 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2019",

month = mar,

day = "15",

doi = "10.1126/science.aau0964",

language = "English",

volume = "363",

journal = "Science",

issn = "0036-8075",

publisher = "AMER ASSOC ADVANCEMENT SCIENCE",

number = "6432",

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Chakarov, S, Lim, HY, Tan, L, Lim, SY, See, P, Lum, J, Zhang, X-M, 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, S-AES, Schlitzer, A, Larbi, A, Marichal, T, Malissen, B, Chen, J, Poidinger, M, Kabashima, K, Bajenoff, M, Ng, LG, Angeli, V & Ginhoux, F 2019, 'Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches', Science, vol. 363, no. 6432, eaau0964. https://doi.org/10.1126/science.aau0964

TY - JOUR

T1 - Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches

AU - Chakarov, Svetoslav

AU - Lim, Hwee Ying

AU - Tan, Leonard

AU - Lim, Sheau Yng

AU - See, Peter

AU - Lum, Josephine

AU - Zhang, Xiao-Meng

AU - Foo, Shihui

AU - Nakamizo, Satoshi

AU - Duan, Kaibo

AU - Kong, Wan Ting

AU - Gentek, Rebecca

AU - Balachander, Akhila

AU - Carbajo, Daniel

AU - Bleriot, Camille

AU - Malleret, Benoit

AU - Tam, John Kit Chung

AU - Baig, Sonia

AU - Shabeer, Muhammad

AU - Toh, Sue-Anne Ee Shiow

AU - Schlitzer, Andreas

AU - Larbi, Anis

AU - Marichal, Thomas

AU - Malissen, Bernard

AU - Chen, Jinmiao

AU - Poidinger, Michael

AU - Kabashima, Kenji

AU - Bajenoff, Marc

AU - Ng, Lai Guan

AU - Angeli, Veronique

AU - Ginhoux, Florent

PY - 2019/3/15

Y1 - 2019/3/15

N2 - 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 (Slco2b1flox/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.

AB - 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 (Slco2b1flox/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.

KW - Animals

KW - Antigens, Ly

KW - CX3C Chemokine Receptor 1/genetics

KW - Cell Lineage

KW - Dermis/immunology

KW - Disease Models, Animal

KW - Fibrosis

KW - Glycoproteins/analysis

KW - Histocompatibility Antigens Class II/genetics

KW - Lung/immunology

KW - Macrophages/immunology

KW - Membrane Transport Proteins

KW - Mice

KW - Mice, Inbred C57BL

KW - Monocytes/immunology

KW - Myocardium/immunology

KW - Organic Anion Transporters/genetics

KW - Sequence Analysis, RNA/methods

KW - Single-Cell Analysis/methods

KW - Transcriptome

U2 - 10.1126/science.aau0964

DO - 10.1126/science.aau0964

M3 - Article

C2 - 30872492

SN - 0036-8075

VL - 363

JO - Science

JF - Science

IS - 6432

M1 - eaau0964

ER -

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

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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Rebecca Gentek

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