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Elife. 2019 Mar 26;8. pii: e42025. doi: 10.7554/eLife.42025.

Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter.

Author information

1
Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, Japan.
2
Division of Brain Structure and Function, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
3
Research Center for Child Mental Development, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
4
Life Science Innovation Center, University of Fukui, Fukui, Japan.
5
Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, Assiut University, Asyut, Egypt.
6
Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
7
Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Gunma, Japan.
8
Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, Umeå, Sweden.
9
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

Abstract

A characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein α (SIRPα), a membrane protein, induced the emergence of CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRPα, and microglia-specific SIRPα-knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRPα and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPα did not cause detectable damage to the white matter, but resulted in the increased expression of genes whose expression is characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.

KEYWORDS:

CD11c; demyelination; microglia; mouse; neuroscience; tissue repair; white matter

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