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 journalArticlepeer-review

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.
Original languageEnglish
Article numbereaau0964
JournalScience
Volume363
Issue number6432
DOIs
Publication statusPublished - 15 Mar 2019

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

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