MiR-1165-3p Suppresses Th2 Differentiation via Targeting IL-13 and PPM1A in a Mouse Model of Allergic Airway Inflammation

作者：Zhengxia Wang, Ningfei Ji, Zhongqi Chen, Zhixiao Sun, Chaojie Wu, Wenqing Yu, Fan Hu, Mao Huang, Mingshun Zhang · 发表于：Allergy Asthma and Immunology Research · 年份：2020 · DOI：10.4168/aair.2020.12.5.859 · 被引用次数：21 · 研究领域：Asthma and respiratory diseases、IL-33, ST2, and ILC Pathways、Fatty Acid Research and Health

PURPOSE: CD4⁺T cells are essential in the pathogenesis of allergic asthma. We have previously demonstrated that microRNA-1165-3p (miR-1165-3p) was significantly reduced in T-helper type (Th) 2 cells and that miR-1165-3p was a surrogate marker for atopic asthma. Little is known about the mechanisms of miR-1165-3p in the regulation of Th2-dominated allergic inflammation. We aimed to investigate the associations between Th2 differentiation and miR-1165b-3p in asthma as well as the possible mechanisms. METHODS: -dependent 1A (PPM1A), in Th2 cell differentiation and allergic asthma were further explored. Plasma PPM1A was determined by ELISA in 18 subjects with asthma and 20 controls. RESULTS: . In contrast, miR-1165-3p silencing promoted Th2-cell development. In the HDM-induced model of allergic airway inflammation, miR-1165-3p up-regulation was accompanied by reduced airway hyper-responsiveness, serum immunoglobulin E, airway inflammation and Th2-cell polarization. IL-13 and PPM1A were the direct targets of miR-1165-3p. The expression of IL-13 or PPM1A was inversely correlated with that of miR-1165-3p. PPM1A regulated the signal transducer and activator of transcription and AKT signaling pathways during Th2 differentiation. Moreover, plasma PPM1A was significantly increased in asthmatic patients. CONCLUSIONS: MiR-1165-3p negatively may regulate Th2-cell differentiation by targeting IL-13 and PPM1A in allergic airway inflammation.