MiR-493-5p inhibits Th9 cell differentiation in allergic asthma by targeting FOXO1

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作者
Xingyu Rao
Heting Dong
Weili Zhang
Huiming Sun
Wenjing Gu
Xinxing Zhang
Li Huang
Yongdong Yan
Chuangli Hao
Wei Ji
Canhong Zhu
Zhengrong Chen
机构
[1] Children’s Hospital of Soochow University,Department of Respiratory Medicine
[2] First Affiliated Hospital of Gannan Medical University,undefined
来源
Respiratory Research | / 23卷
关键词
Asthma; FOXO1; miR-493-5p; Th9 cell differentiation; Exosomes;
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摘要
The role of micro RNAs (miRNAs) in asthma remains unclear. In this study, we examined the role of miRNA in targeting FOXO1 in asthma. Results showed that miR-493-5p was one of the differentially expressed miRNAs in the PBMCs of asthmatic children, and was also associated with Th cell differentiation. The miR-493-5p expression decreased significantly in the OVA-induced asthma mice than the control groups. The miR-493-5p mimic inhibited the expression of the IL-9, IRF4 and FOXO1, while the inhibitor restored these effects. Moreover, the Dual-Luciferase analysis results showed FOXO1 as a novel valid target of miR-493-5p. According to the rescue experiment, miR-493-5p inhibited Th9 cell differentiation by targeting FOXO1. Then the exosomes in association with the pathogenesis of asthma was identified. Various inflammatory cells implicated in asthmatic processes including B and T lymphocytes, DCs, mast cells, and epithelial cells can release exosomes. Our results demonstrated that the DC-derived exosomes can inhibit Th9 cell differentiation through miR-493-5p, thus DC-derived exosomal miR-493-5p/FOXO1/Th9 may serve as a potential therapeutic target in the development of asthma.
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