GPR34 senses demyelination to promote neuroinflammation and pathologies.
Cell Mol Immunol
; 2024 Jul 19.
Article
em En
| MEDLINE
| ID: mdl-39030423
ABSTRACT
Sterile neuroinflammation is a major driver of multiple neurological diseases. Myelin debris can act as an inflammatory stimulus to promote inflammation and pathologies, but the mechanism is poorly understood. Here, we showed that lysophosphatidylserine (LysoPS)-GPR34 axis played a critical role in microglia-mediated myelin debris sensing and the subsequent neuroinflammation. Myelin debris-induced microglia activation and proinflammatory cytokine expression relied on its lipid component LysoPS. Both myelin debris and LysoPS promoted microglia activation and the production of proinflammatory cytokines via GPR34 and its downstream PI3K-AKT and ERK signaling. In vivo, reducing the content of LysoPS in myelin or inhibition of GPR34 with genetic or pharmacological approaches reduced neuroinflammation and pathologies in the mouse models of multiple sclerosis and stroke. Thus, our results identify GPR34 as a key receptor to sense demyelination and CNS damage and promote neuroinflammation, and suggest it as a potential therapeutic target for demyelination-associated diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cell Mol Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
CHINA
/
CN
/
REPUBLIC OF CHINA