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

Sato-Hashimoto, M.; Nozu, T.; Toriba, R.; Horikoshi, A.; Akaike, M.; Kawamoto, K.; Hirose, A.; Hayashi, Y.; Nagai, H.; Shimizu, W.; Saiki, A.; Ishikawa, T.; Elhanbaly, R.; Kotani, T.; Murata, Y.; Saito, Y.; Masae, M.; Shibasaki, K.; Oldenborg, P.-A.; Jung, S.; Matozaki, T.; Fukazawa, Y.; Ohnishi, H.

doi:10.1101/443531

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bioRxiv · 10.1101/443531

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

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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 (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.

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Sato-Hashimoto, M., Nozu, T., Toriba, R., Horikoshi, A., Akaike, M., Kawamoto, K., Hirose, A., Hayashi, Y., Nagai, H., Shimizu, W., Saiki, A., Ishikawa, T., Elhanbaly, R., Kotani, T., Murata, Y., Saito, Y., Masae, M., Shibasaki, K., Oldenborg, P.-A., Jung, S., Matozaki, T., Fukazawa, Y., Ohnishi, H.. 2018-10-24. Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter. https://doi.org/10.1101/443531

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