Journal
ISCIENCE
Volume 23, Issue 9, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2020.101520
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Funding
- Ministry of Education, Science and Technology (MEXT)
- Japan Agency for Medical Research and Development (AMED)
- JSPS KAKENHI [18K07325]
- Takeda Science Foundation
- Kumamoto University Advance Research Project A International Research Center for Cancer and Metabolism
- Grants-in-Aid for Scientific Research [18K07325] Funding Source: KAKEN
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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.
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