Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter
2019
A characteristic subset of
microgliaexpressing
CD11cappears 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
CD11c+
microgliain the brain
white matter. Mice lacking
CD47, a physiological ligand of SIRPα, and
microglia-specific SIRPα knockout mice exhibited the same phenotype, suggesting the interaction between microglial SIRPα and
CD47on neighbouring cells suppressed the emergence of
CD11c+
microglia. A lack of SIRPα 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 SIRPα. Thus, microglial SIRPα suppresses the induction of
CD11c+
microgliathat have the potential to accelerate the repair of damaged
white matter.
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