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Nat Immunol. 2016 Jul;17(7):797-805. doi: 10.1038/ni.3423. Epub 2016 May 2.

Origin, fate and dynamics of macrophages at central nervous system interfaces.

Author information

1
Institute of Neuropathology, Freiburg University Medical Centre, Freiburg, Germany.
2
Faculty of Biology, University of Freiburg, Freiburg, Germany.
3
Institute of Anatomy, University of Leipzig, Leipzig, Germany.
4
Institut für Klinische Neuroimmunologie, Ludwig-Maximilians Universität München, Munich, Germany.
5
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
6
Department of Hematology and Oncology, Freiburg University Medical Centre, Freiburg, Germany.
7
BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany.
8
Peter Munk Cardiac Centre, University Health Network Toronto, Ontario, Canada.
9
Centre for Molecular and Cellular Biology of Inflammation, King's College London, London, UK.
10
Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité - Universitätsmedizin Berlin; Cluster of Excellence NeuroCure, DZNE &BIH, Berlin, Germany.
11
The Biomedical Research Centre, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
12
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
13
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.

Abstract

Perivascular, subdural meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It was assumed that they have a high turnover from blood-borne monocytes. However, using parabiosis and fate-mapping approaches in mice, we found that CNS macrophages arose from hematopoietic precursors during embryonic development and established stable populations, with the notable exception of choroid plexus macrophages, which had dual origins and a shorter life span. The generation of CNS macrophages relied on the transcription factor PU.1, whereas the MYB, BATF3 and NR4A1 transcription factors were not required.

Comment in

PMID:
27135602
PMCID:
PMC4968048
DOI:
10.1038/ni.3423
[Indexed for MEDLINE]
Free PMC Article

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