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外泌体在免疫病理学中的作用及潜在治疗意义。

The role of exosomes in immunopathology and potential therapeutic implications.

作者信息

Wang Wenhui, Qiao Shuya, Kong Xianghui, Zhang Gensheng, Cai Zhijian

机构信息

Department of Orthopedics of the Second Affiliated Hospital and Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.

Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Cell Mol Immunol. 2025 Jul 14. doi: 10.1038/s41423-025-01323-5.

DOI:10.1038/s41423-025-01323-5
PMID:40659888
Abstract

Extracellular vesicles (EVs), including exosomes, ectosomes, and apoptotic bodies, are released by various cells. Among these subtypes, exosomes have been extensively studied and demonstrated to be crucial mediators of intercellular communication involving multiple physiological and pathological processes. Four primary steps influence the biogenesis of exosomes: generation of early endosomes, formation and maturation of multivesicular bodies (MVBs), MVB and plasma membrane fusion for exosome release, and MVB fusion with lysosomes for degradation. During the formation and maturation of MVBs, the main effector molecules, such as RNAs and proteins, are sorted into exosomes via diverse mechanisms. However, the effector molecules of exosomes are dynamic and reflect cell states in real time. Therefore, exosomes secreted by cells under disease conditions are often pathogenic. This review focuses on recent advances in the understanding of exosome biogenesis and the immunopathological effects of exosomes. In addition, potential strategies to mitigate the pathological effects of exosomes are summarized in this review.

摘要

细胞外囊泡(EVs),包括外泌体、微泡和凋亡小体,由各种细胞释放。在这些亚型中,外泌体已得到广泛研究,并被证明是涉及多种生理和病理过程的细胞间通讯的关键介质。影响外泌体生物发生的主要有四个步骤:早期内体的产生、多泡体(MVBs)的形成和成熟、MVB与质膜融合以释放外泌体,以及MVB与溶酶体融合以进行降解。在MVB的形成和成熟过程中,主要的效应分子,如RNA和蛋白质,通过多种机制被分选到外泌体中。然而,外泌体的效应分子是动态的,实时反映细胞状态。因此,疾病状态下细胞分泌的外泌体往往具有致病性。本综述重点介绍了对外泌体生物发生的最新认识以及外泌体的免疫病理效应。此外,本综述还总结了减轻外泌体病理效应的潜在策略。

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本文引用的文献

1
MFGE8 induces anti-PD-1 therapy resistance by promoting extracellular vesicle sorting of PD-L1.MFGE8通过促进PD-L1的细胞外囊泡分选来诱导抗PD-1治疗耐药性。
Cell Rep Med. 2025 Feb 18;6(2):101922. doi: 10.1016/j.xcrm.2024.101922. Epub 2025 Jan 21.
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Uterine-derived exosomes induce the M2 polarization of macrophages via miR-210-3p/ATP5D to promote endometriosis progression.子宫来源的外泌体通过miR-210-3p/ATP5D诱导巨噬细胞的M2极化,以促进子宫内膜异位症进展。
Life Sci. 2025 Feb 15;363:123383. doi: 10.1016/j.lfs.2025.123383. Epub 2025 Jan 9.
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Substrate stiffness regulates the proliferation and inflammation of chondrocytes and macrophages through exosomes.
底物硬度通过外泌体调节软骨细胞和巨噬细胞的增殖与炎症反应。
Acta Biomater. 2025 Jan 15;192:77-89. doi: 10.1016/j.actbio.2024.12.021. Epub 2024 Dec 9.
4
Macrophage exosomal miR-30c-2-3p in atherosclerotic plaques aggravates microglial neuroinflammation during large-artery atherosclerotic stroke via TGF-β/SMAD2 pathway.载瘤巨噬细胞外泌体 miR-30c-2-3p 通过 TGF-β/SMAD2 通路加重大动脉粥样硬化性脑梗死时小胶质细胞神经炎症。
J Neuroinflammation. 2024 Nov 8;21(1):292. doi: 10.1186/s12974-024-03281-7.
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The endosomal-vacuolar transport system acts as a docking platform for the Pmk1 MAP kinase signaling pathway in Magnaporthe oryzae.内体-液泡转运系统充当稻瘟病菌中Pmk1丝裂原活化蛋白激酶信号通路的对接平台。
New Phytol. 2025 Jan;245(2):722-747. doi: 10.1111/nph.20235. Epub 2024 Nov 4.
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Exosomal miR-129-2-3p promotes airway epithelial barrier disruption in PM-aggravated asthma.外泌体miR-129-2-3p促进颗粒物加重型哮喘中气道上皮屏障的破坏。
J Environ Manage. 2024 Nov;370:123053. doi: 10.1016/j.jenvman.2024.123053. Epub 2024 Oct 28.
7
Study of the mechanism of fibroblast-like synoviocytes-derived exosomes inducing macrophages M1 polarization and CD8T cells immune regulation ferroptosis and autophagy in rheumatoid arthritis.类风湿关节炎中滑膜成纤维样细胞来源的外泌体诱导巨噬细胞M1极化及CD8⁺T细胞免疫调节性铁死亡和自噬的机制研究
Immunol Lett. 2024 Dec;270:106936. doi: 10.1016/j.imlet.2024.106936. Epub 2024 Oct 22.
8
Trophoblast cell-derived extracellular vesicles regulate the polarization of decidual macrophages by carrying miR-141-3p in the pathogenesis of preeclampsia.滋养层细胞衍生的细胞外囊泡通过携带 miR-141-3p 在子痫前期发病机制中调节蜕膜巨噬细胞的极化。
Sci Rep. 2024 Oct 18;14(1):24529. doi: 10.1038/s41598-024-76563-y.
9
Neutrophil N1 polarization induced by cardiomyocyte-derived extracellular vesicle miR-9-5p aggravates myocardial ischemia/reperfusion injury.心肌细胞来源的细胞外囊泡 miR-9-5p 诱导的中性粒细胞 N1 极化加重心肌缺血/再灌注损伤。
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10
Clathrin-associated carriers enable recycling through a kiss-and-run mechanism.网格蛋白相关载体通过亲吻-跑离机制实现循环。
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