Deciphering the heterogeneity of the Lyve1+ perivascular macrophages in the mouse brain

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • C Siret - , Aix-Marseille Université (Author)
  • M van Lessen - , University of Münster (Author)
  • J Bavais - , Aix-Marseille Université (Author)
  • H W Jeong - , Max Planck Institute for Molecular Biomedicine (Author)
  • S K Reddy Samawar - , University of Münster (Author)
  • K Kapupara - , University of Münster (Author)
  • S Wang - , Aix-Marseille Université, Université de Bordeaux, INSERM - Institut national de la santé et de la recherche médicale, Centre d'Immunologie de Marseille-Luminy (CIML) (Author)
  • M Simic - , Aix-Marseille Université (Author)
  • L de Fabritus - , Aix-Marseille Université (Author)
  • A Tchoghandjian - , Aix-Marseille Université (Author)
  • M Fallet - , Aix-Marseille Université (Author)
  • H Huang - , Center for Regenerative Therapies Dresden, Chair of Stem Cell Research with focus on cell-based approaches to regenerative biomedicine, Aix-Marseille Université, Université de Bordeaux, INSERM - Institut national de la santé et de la recherche médicale, Centre d'Immunologie de Marseille-Luminy (CIML) (Author)
  • S Sarrazin - , Aix-Marseille Université (Author)
  • M H Sieweke - , Center for Regenerative Therapies Dresden, Chair of Stem Cell Research with focus on cell-based approaches to regenerative biomedicine, Aix-Marseille Université, Université de Bordeaux, INSERM - Institut national de la santé et de la recherche médicale, Centre d'Immunologie de Marseille-Luminy (CIML) (Author)
  • R Stumm - , Jena University Hospital (Author)
  • L Sorokin - , University of Münster (Author)
  • R H Adams - , Max Planck Institute for Molecular Biomedicine (Author)
  • S Schulte-Merker - , University of Münster (Author)
  • F Kiefer - , Max Planck Institute for Molecular Biomedicine (Author)
  • S A van de Pavert - , Aix-Marseille Université (Author)

Abstract

Perivascular macrophages (pvMs) are associated with cerebral vasculature and mediate brain drainage and immune regulation. Here, using reporter mouse models, whole brain and section immunofluorescence, flow cytometry, and single cell RNA sequencing, besides the Lyve1+F4/80+CD206+CX3CR1+ pvMs, we identify a CX3CR1- pvM population that shares phagocytic functions and location. Furthermore, the brain parenchyma vasculature mostly hosts Lyve1+MHCII- pvMs with low to intermediate CD45 expression. Using the double Cx3cr1GFP x Cx3cr1-Cre;RosatdT reporter mice for finer mapping of the lineages, we establish that CD45lowCX3CR1- pvMs are derived from CX3CR1+ precursors and require PU.1 during their ontogeny. In parallel, results from the Cxcr4-CreErt2;Rosa26tdT lineage tracing model support a bone marrow-independent replenishment of all Lyve1+ pvMs in the adult mouse brain. Lastly, flow cytometry and 3D immunofluorescence analysis uncover increased percentage of pvMs following photothrombotic induced stroke. Our results thus show that the parenchymal pvM population is more heterogenous than previously described, and includes a CD45low and CX3CR1- pvM population.

Details

Original languageEnglish
Article number7366
JournalNature communications
Volume13
Issue number1
Publication statusPublished - 30 Nov 2022
Peer-reviewedYes

External IDs

PubMedCentral PMC9712536
Scopus 85143075125
unpaywall 10.1038/s41467-022-35166-9

Keywords

Keywords

  • Animals, Mice, Macrophages, Leukocyte Count, Phagocytes, Flow Cytometry, Brain