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GPR34 senses demyelination to promote neuroinflammation and pathologies

Bolong Lin1, Yubo Zhou1, Zonghui Huang1,2

  • 1Key Laboratory of immune response and immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.

Cellular & Molecular Immunology
|July 19, 2024
PubMed

Insights

Myelin debris triggers sterile neuroinflammation via lysophosphatidylserine (LysoPS) activating the GPR34 receptor on microglia. Inhibiting this pathway reduces neurological disease pathology.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Sterile neuroinflammation drives neurological diseases.
  • Myelin debris is an inflammatory stimulus, but its mechanism is unclear.

Purpose of the Study:

  • Investigate the role of the lysophosphatidylserine (LysoPS)-GPR34 axis in microglia-mediated myelin debris sensing and neuroinflammation.

Main Methods:

  • Assessed microglia activation and cytokine expression in response to myelin debris and LysoPS.
  • Utilized in vivo mouse models of multiple sclerosis and stroke.
  • Employed genetic and pharmacological inhibition of GPR34.

Main Results:

  • Myelin debris-induced neuroinflammation depends on its lipid component, LysoPS.
  • LysoPS and myelin debris activate microglia and promote cytokine production via GPR34 and PI3K-AKT/ERK signaling.
  • Inhibition of GPR34 or reduction of LysoPS content ameliorated neuroinflammation and pathology in mouse models.

Conclusions:

  • The GPR34 receptor is crucial for sensing demyelination and central nervous system damage.
  • The LysoPS-GPR34 pathway promotes neuroinflammation.
  • GPR34 is a potential therapeutic target for demyelination-associated diseases.
Keywords:
GPCRsMicrogliaNeuroinflammation

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