Aging-Associated Extracellular Vesicles Contain Immune Regulatory microRNAs Alleviating Hyperinflammatory State and Immune Dysfunction in the Elderly
Aging-Associated Extracellular Vesicles Contain Immune Regulatory microRNAs Alleviating Hyperinflammatory State and Immune Dysfunction in the Elderly
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DOI：
10.1016/j.isci.2020.101520
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发表时间：
2020-09
期刊：
影响因子：
5.8
通讯作者：
Hirotake Tsukamoto;T. Kouwaki;H. Oshiumi
中科院分区：
文献类型：
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作者：
Hirotake Tsukamoto;T. Kouwaki;H. Oshiumi
免疫系统中与衰老相关的变化通常会导致免疫功能障碍;然而，这种现象背后的机制尚未完全阐明。这项研究发现，microRNA-192（miR-192）是一种与衰老相关的免疫调节microRNA，由于老年小鼠的高炎症状态，其浓度在老年细胞外囊泡（EV）中显著增加。有趣的是，EV miR-192对巨噬细胞表现出抗炎作用。在我们的老年小鼠模型中，衰老与用灭活流感全病毒颗粒（WVP）刺激后肺中的长期炎症相关，而EV miR-192减轻了与衰老相关的长期炎症。老年小鼠的高炎症状态导致特异性抗体的产生和WVP疫苗接种的效力降低;然而，EV miR-192减弱了这种高炎症状态并改善了老年小鼠的疫苗接种效力。我们的数据表明，老化的电动汽车构成了一个负反馈回路，加剧了衰老相关的免疫功能障碍。
Aging-associated changes in the immune system often lead to immune dysfunction; however, the mechanisms that underlie this phenomenon have yet to be fully elucidated. This study found that the microRNA-192 (miR-192) is an aging-associated immune regulatory microRNA whose concentration was significantly increased in aged extracellular vesicles (EVs) due to the hyperinflammatory state of aged mice. Interestingly, EV miR-192 exhibited anti-inflammatory effects on macrophages. In our aged mouse model, aging was associated with prolonged inflammation in the lung upon stimulation with inactivated influenza whole virus particles (WVP), whereas EV miR-192 alleviated the prolonged inflammation associated with aging. The hyperinflammatory state of aged mice resulted in reduced production of specific antibodies and efficacy of vaccination with WVP; however, EV miR-192 attenuated this hyperinflammatory state and improved vaccination efficacy in aged mice. Our data indicate that aged EVs constitute a negative feedback loop that alleviates aging-associated immune dysfunction.