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

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 (SIRP ), a membrane pro...

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Published inbioRxiv
Main Authors Sato-Hashimoto, Miho, Nozu, Tomomi, Toriba, Riho, Horikoshi, Ayano, Akaike, Miho, Kawamoto, Kyoko, Hirose, Ayaka, Hayashi, Yuriko, Nagai, Hiromi, Shimizu, Wakana, Saiki, Ayaka, Ishikawa, Tatsuya, Elhanbaly, Ruwaida, Kotani, Takenori, Murata, Yoji, Saito, Yasuyuki, Naruse, Masae, Shibasaki, Koji, Pre-Arne Oldenborg, Jung, Steffen, Matozaki, Takashi, Fukazawa, Yugo, Ohnishi, Hiroshi
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 24.10.2018
Subjects
Brain injury
CD11c antigen
Cuprizone
Demyelination
Membrane proteins
Microglia
Phenotypes
Substantia alba
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Summary: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 (SIRP ), a membrane protein, induced CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRP , and microglia-specific SIRP knockout mice exhibited the same phenotype, suggesting the interaction between microglial SIRP and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRP did not cause detectable damage in the white matter, but resulted in the increased expression of genes characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRP . Thus, microglial SIRP suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter. Footnotes * A spelling mistake in the name of one author is corrected.
DOI:10.1101/443531