GPR34 senses demyelination to promote neuroinflammation and pathologies  

作　　者：Bolong Lin Yubo Zhou Zonghui Huang Ming Ma Minghui Qi Zhongjun Jiang Guoyang Li Yueli Xu Jiaxian Yan Di Wang Xiaqiong Wang Wei Jiang Rongbin Zhou 

机构地区：[1]Key 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 [2]Hefei National Research Center for Physical Sciences at the Microscale,University of Science and Technology of China,Hefei,Anhui,China [3]Institute of Immunology,Zhejiang University School of Medicine,Hangzhou,China [4]Department of Geriatrics,Gerontology Institute of Anhui Province,The First Affiliated Hospital of University of Science and Technology of China,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,China

出　　处：《Cellular & Molecular Immunology》2024年第10期1131-1144,共14页中国免疫学杂志（英文版）

基　　金：supported by the National Key Research and Development Program of China(grant number 2020YFA0509101);the National Natural Science Foundation of China(grant numbers 81821001,82130107,U20A20359);the CAS Project for Young Scientists in Basic Research(YSBR-074).

摘　　要：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.

关 键 词：NEUROINFLAMMATION GPCRS MICROGLIA 

分 类 号：R745[医药卫生—神经病学与精神病学]