Tsukamoto Hirotake, Kouwaki Takahisa, Oshiumi Hiroyuki
Department of Immunology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
iScience. 2020 Sep 1;23(9):101520. doi: 10.1016/j.isci.2020.101520. eCollection 2020 Sep 25.
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.
免疫系统中与衰老相关的变化常常导致免疫功能障碍；然而，这一现象背后的机制尚未完全阐明。本研究发现，微小RNA - 192（miR - 192）是一种与衰老相关的免疫调节性微小RNA，由于老年小鼠的高炎症状态，其在衰老细胞外囊泡（EVs）中的浓度显著增加。有趣的是，EV miR - 192对巨噬细胞具有抗炎作用。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）刺激后肺部炎症的延长有关，而EV miR - 192减轻了与衰老相关的炎症延长。老年小鼠的高炎症状态导致特异性抗体产生减少以及WVP疫苗接种效果降低；然而，EV miR - 192减弱了这种高炎症状态并提高了老年小鼠的疫苗接种效果。我们的数据表明，衰老的EVs构成了一个负反馈回路，可减轻与衰老相关的免疫功能障碍。
