细胞外小泡
视神经脊髓炎
光谱紊乱
细胞外
微泡
医学
免疫学
神经科学
病毒学
病理
化学
生物
细胞生物学
多发性硬化
小RNA
精神科
生物化学
基因
作者
Shihe Jiang,X. N. Li,Y. Li,Zhilin Chang,Meng Yuan,Ying Zhang,Huimin Zhu,Yuwen Xiu,Hengri Cong,Linlin Yin,Zhenwei Yu,Junwan Fan,Wenyan He,Kaibin Shi,De-Cai Tian,Jing Zhang,Alexei Verkhratsky,Wen Jin,Fu‐Dong Shi
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2024-02-28
卷期号:16 (736)
标识
DOI:10.1126/scitranslmed.adg5116
摘要
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy of the central nervous system, mediated by antibodies against aquaporin-4 water channel protein (AQP4-Abs), resulting in damage of astrocytes with subsequent demyelination and axonal damage. Extracellular communication through astrocyte-derived extracellular vesicles (ADEVs) has received growing interest in association with astrocytopathies. However, to what extent ADEVs contribute to NMOSD pathogenesis remains unclear. Here, through proteomic screening of patient-derived ADEVs, we observed an increase in apolipoprotein E (APOE)–rich ADEVs in patients with AQP4-Abs–positive NMOSD. Intracerebral injection of the APOE-mimetic peptide APOE 130–149 attenuated microglial reactivity, neuroinflammation, and brain lesions in a mouse model of NMOSD. The protective effect of APOE in NMOSD pathogenesis was further established by the exacerbated lesion volume in APOE-deficient mice, which could be rescued by exogenous APOE administration. Genetic knockdown of the APOE receptor lipoprotein receptor–related protein 1 (LRP1) could block the restorative effects of APOE 130–149 administration. The transfusion ADEVs derived from patients with NMOSD and healthy controls also alleviated astrocyte loss, reactive microgliosis, and demyelination in NMOSD mice. The slightly larger beneficial effect of patient-derived ADEVs as compared to ADEVs from healthy controls was further augmented in APOE −/− mice. These results indicate that APOE from astrocyte-derived extracellular vesicles could mediate disease-modifying astrocyte-microglia cross-talk in NMOSD.
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