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

Author

Listed:
  • C. Siret

    (Aix-Marseille Univ, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy (CIML))

  • M. Lessen

    (University of Münster)

  • J. Bavais

    (Aix-Marseille Univ, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy (CIML)
    Turing Centre for Living systems)

  • H. W. Jeong

    (Max Planck Institute for Molecular Biomedicine)

  • S. K. Reddy Samawar

    (University of Münster)

  • K. Kapupara

    (University of Münster)

  • S. Wang

    (Aix-Marseille Univ, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy (CIML))

  • M. Simic

    (Aix-Marseille Univ, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy (CIML))

  • L. Fabritus

    (Aix-Marseille Univ, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy (CIML))

  • A. Tchoghandjian

    (Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol)

  • M. Fallet

    (Aix-Marseille Univ, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy (CIML))

  • H. Huang

    (Aix-Marseille Univ, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy (CIML)
    Technische Universität Dresden)

  • S. Sarrazin

    (Aix-Marseille Univ, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy (CIML))

  • M. H. Sieweke

    (Aix-Marseille Univ, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy (CIML)
    Technische Universität Dresden)

  • R. Stumm

    (Jena University Hospital)

  • L. Sorokin

    (University of Münster)

  • R. H. Adams

    (Max Planck Institute for Molecular Biomedicine)

  • S. Schulte-Merker

    (University of Münster)

  • F. Kiefer

    (Max Planck Institute for Molecular Biomedicine
    University of Münster, European Institute for Molecular Imaging (EIMI) and Cells in Motion Interfaculty Centre (CIMIC))

  • S. A. Pavert

    (Aix-Marseille Univ, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy (CIML))

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.

Suggested Citation

  • C. Siret & M. Lessen & J. Bavais & H. W. Jeong & S. K. Reddy Samawar & K. Kapupara & S. Wang & M. Simic & L. Fabritus & A. Tchoghandjian & M. Fallet & H. Huang & S. Sarrazin & M. H. Sieweke & R. Stumm, 2022. "Deciphering the heterogeneity of the Lyve1+ perivascular macrophages in the mouse brain," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35166-9
    DOI: 10.1038/s41467-022-35166-9
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    1. Ji Hoon Ahn & Hyunsoo Cho & Jun-Hee Kim & Shin Heun Kim & Je-Seok Ham & Intae Park & Sang Heon Suh & Seon Pyo Hong & Joo-Hye Song & Young-Kwon Hong & Yong Jeong & Sung-Hong Park & Gou Young Koh, 2019. "Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid," Nature, Nature, vol. 572(7767), pages 62-66, August.
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