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

Miho Sato-Hashimoto1, Tomomi Nozu1, Riho Toriba1

  • 1Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, Japan.

Elife
|March 27, 2019
PubMed

Insights

Signal regulatory protein α (SIRPα) on microglia normally suppresses CD11c expression. Removing SIRPα promotes CD11c+ microglia, enhancing white matter repair after demyelination.

Area of Science:

  • Neuroimmunology
  • Cellular Biology
  • Neuroinflammation

Background:

  • Microglia, the brain's immune cells, exhibit specific phenotypes in response to injury.
  • A subset of microglia expressing CD11c is observed after brain damage, but their function and induction mechanisms remain unclear.

Purpose of the Study:

  • To investigate the role of signal regulatory protein α (SIRPα) in the induction of CD11c+ microglia.
  • To elucidate the mechanism by which SIRPα influences microglial phenotype and white matter repair.

Main Methods:

  • Genetic ablation of SIRPα in mice.
  • Analysis of CD11c expression in microglia.
  • Investigating the CD47-SIRPα interaction.
  • Assessing gene expression related to white matter repair.
  • Evaluating cuprizone-induced demyelination models.

Main Results:

  • Genetic deletion of SIRPα in mice led to the emergence of CD11c+ microglia in white matter.
  • Absence of CD47, the ligand for SIRPα, mimicked the SIRPα knockout phenotype.
  • Microglial SIRPα, through interaction with CD47, suppresses CD11c+ microglia induction.
  • SIRPα deficiency enhanced gene expression associated with white matter repair.
  • Microglia-specific SIRPα ablation alleviated cuprizone-induced demyelination.

Conclusions:

  • Microglial SIRPα acts as a suppressor of CD11c+ microglia induction.
  • CD11c+ microglia, promoted by SIRPα deficiency, possess the potential to accelerate white matter repair.
  • Targeting the SIRPα-CD47 pathway may offer therapeutic strategies for demyelinating diseases.
Keywords:
CD11cdemyelinationmicrogliamouseneurosciencetissue repairwhite matter

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