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

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 a (SIRPa), a membrane protein, induced the emergence of CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRPa, and microglia-specific SIRPa- knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRPa and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPa 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 SIRPa. Thus, microglial SIRPa suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.