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IL-27 Alleviates Airway Inflammation and Airway Hyperresponsiveness in Asthmatic Mice by Targeting the CD39/ATP Axis of Dendritic Cells
Inflammation ( IF 4.5 ) Pub Date : 2023-12-20 , DOI: 10.1007/s10753-023-01945-9
Yifei Chen 1 , Miaojuan Zhu 1 , Jiahao Hu 2 , Shaojun He 1 , Shuhua Li 1 , Bing Liu 1 , Jiong Yang 1
Affiliation  

Interleukin-27 receptor (IL-27R) is expressed in a variety of immune cells and structural cells, including dendritic cells. The mechanism of IL-27 in asthma has not been fully elucidated. This study aimed to examine whether IL-27 regulated the CD39/ATP axis of dendritic cells in asthma. Our results showed that in ovalbumin (OVA)-induced asthma mouse model, IL-27Rα−/− asthmatic mice showed increased airway resistance, increased infiltration of inflammatory cells in lung tissue, proliferation of goblet cells, enhanced expression of Muc5 AC around airway epithelium, increased total number of cells and eosinophils, increased levels of total IgE, OVA-IgE, IL-4, IL-5, IL-13 and IL-17 A, and increased expression of transcription factors GATA-3 and RORγt in lung tissue. The expression of CD39 mRNA and protein in the lung tissue of IL-27Rα−/− asthmatic mice decreased, and the expression of NLRP3, ASC and Caspase-1 in NLRP3 inflammasome components increased. The concentration of ATP was significantly increased compared with WT asthmatic mice. In vitro experiments showed that the expression of CD39 in lung dendritic cells of IL-27Rα−/− asthmatic mice decreased, while the expression of NLRP3 inflammasome components NLRP3, ASC and Caspase-1 increased. These findings indicate that IL-27 directly and indirectly regulates immunoinflammatory responses in asthma by acting on dendritic cells CD39/ATP Axis.



中文翻译:


IL-27 通过靶向树突状细胞的 CD39/ATP 轴减轻哮喘小鼠的气道炎症和气道高反应性



白介素 27 受体 (IL-27R) 在多种免疫细胞和结构细胞(包括树突状细胞)中表达。 IL-27在哮喘中的作用机制尚未完全阐明。本研究旨在探讨 IL-27 是否调节哮喘树突状细胞的 CD39/ATP 轴。我们的结果表明,在卵清蛋白(OVA)诱导的哮喘小鼠模型中,IL-27Rα -/−哮喘小鼠表现出气道阻力增加,肺组织炎症细胞浸润增加,杯状细胞增殖,气道上皮周围 Muc5 AC 表达增强,肺组织中细胞和嗜酸性粒细胞总数增加,总 IgE、OVA-IgE、IL-4、IL-5、IL-13 和 IL-17 A 水平增加,转录因子 GATA-3 和 RORγt 表达增加。 IL-27Rα −/−哮喘小鼠肺组织中CD39 mRNA和蛋白表达量减少,NLRP3炎性体成分中NLRP3、ASC和Caspase-1表达量增加。与WT哮喘小鼠相比,ATP浓度显着升高。体外实验表明,IL-27Rα −/−哮喘小鼠肺树突状细胞中CD39表达减少,而NLRP3炎症小体成分NLRP3、ASC和Caspase-1表达增加。这些发现表明,IL-27 通过作用于树突状细胞 CD39/ATP 轴,直接或间接调节哮喘中的免疫炎症反应。

更新日期:2023-12-20
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