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Journal article

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

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.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-022-35166-9

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
et al.


Publisher:
Springer Nature
Journal:
Nature Communications More from this journal
Volume:
13
Issue:
1
Article number:
7366
Publication date:
2022-11-30
Acceptance date:
2022-11-21
DOI:
EISSN:
2041-1723


Language:
English
Keywords:
Pubs id:
1319802
Local pid:
pubs:1319802
Deposit date:
2023-01-12
ARK identifier:

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