The Mechanism of MiR-181a Overexpression Involved in Regulating Treg Cells Involved in Allergic Rhinitis
Objective To explore the mechanism of miR-181a overexpression in regulating Treg cells to participate in al-lergic rhinitis(AR).Methods 20 children with AR and 20 children with similar age and without allergic history were selected as the research objects.Pearson correlation analysis was used to analyze the relationship between the number of Treg and the expression of miR-181a.The Tregs were purified from PBMCs in AR children.The miR-181a mimics and inhibitors were transfected into Tregs.The function of Tregs were evaluated by flow cytometry and ELISA assay.Mice were divided into 7 groups,with 10 mice in each group:control group,AR group,AR+negative control group,AR+miR-181a simulation group,AR+miR-181a inhibitor group,AR+miR-181a simulation+recombinant OPN protein group,and AR+miR-181a simulation+OPN lentivirus shRNA group.AR models were established using ovalbumin,after which the functional role of miR-181a in AR was determined using gain-and loss-of-function approaches.Results Compared with the control group,the number of Treg and the expression of miR-181a in the PBMCs of patients with AR were significantly decreased.Pearson correlation analysis showed that the number of Treg in PBMCs was positively correlated with the expression of miR-181a(R2=0.335,P＜0.001).MiR-181a mimics promoted the proliferation of Tregs and upregulated the mRNA expression of IL-10 and TGF-β.Luciferase assay showed that miR-181a directly targeted the 3'UTR of OPN.In animal experiments,compared with AR and AR+miR-NC group,the inflammation in AR+miR-181a simulation group was reduced,and the inflammation in AR+miR-181a in-hibitor group was more serious.The recombinant OPN protein significantly reversed the anti-inflammatory effect of miR-181a mimic.In addition,Treg cells in AR group decreased significantly,and miR-181a mimic significantly increased the number of Treg cells in AR mice,while the recombinant OPN protein significantly reversed the increase of Treg cells induced by miR-181a mimic.Conclusion Upregulation of miR-181a significantly decreases the expression of OPN,and subsequently decreases eosinophils and enhances Treg function,by which it contributes to reduce the airway inflammation in the pathogenesis of AR.
miR-181aallergic rhinitismouseregulatory T cellsosteopontin
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