MiR-181a过表达参与调控Treg细胞对儿童变应性鼻炎的机制研究

doi:10.3969/j.issn.1006-6233.2024.07.07

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Abstract Objective: To investigate the expression of miR-181a in the serum of AR children and to analyze the regulatory effect of miR-181a on the differentiation and function of Treg cells in AR patients. Methods: Totally, 20 children with AR and 20 children of similar age without allergic history were selected as the study subjects. Pearson correlation analysis was used to analyze the relationship between the number of peripheral blood Tregs and miR-181a expression. Tregs were purified from the peripheral blood of AR children. miR-181a mimics and inhibitors were transfected into Tregs cells. The function of Tregs was evaluated by flow cytometry and ELISA. An ovalbumin-induced AR mouse model was established, and then the role of miR-181a in AR was determined by gain-of-function and loss-of-function methods. Results: Compared with the control group, the number of peripheral blood Tregs in AR children was decreased, and the expression of miR-181a was significantly decreased. Pearson correlation analysis showed that the number of peripheral blood Tregs was positively correlated with miR-181a expression (R2=0.335, P<0.001). miR-181a mimics promoted the proliferation of Tregs and up-regulated the mRNA expression of IL-10 and TGF-β. Luciferase reporter assay showed that miR-181a directly targeted the 3'UTR of OPN. In animal experiments, compared with the AR and AR+miR-NC groups, the AR+miR-181a mimic group had less inflammation, and the AR+miR-181a inhibitor group had more severe inflammation. Recombinant OPN protein significantly reversed the anti-inflammatory effect of miR-181a mimics. In addition, the number of Treg cells in AR mice was significantly decreased, miR-181a mimics significantly increased the number of Treg cells in AR mice, and recombinant OPN protein significantly reversed the increase of Treg cells induced by miR-181a mimics. Conclusion: The up-regulation of miR-181a significantly reduced the expression of OPN, thereby reducing eosinophils and enhancing Treg function, alleviating the occurrence of airway inflammation during the development of AR.

Key words： Allergic rhinitis MiR-181a Mice Treg Osteopontin

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.07.07 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I7/1094

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