The Impact of IL-18 on the Differentiation of CD4+ Th2 and Th17 Cells and the Expression Levels of IL-18Rα in Lung Tissues of Mice with Allergic Asthma

Objective To investigate the effect of interleukin 18 (IL-18) on the differentiation of CD4 helper cell 2 (Th2) and T helper cell (Th17) and the level of IL-18 receptor α α (IL-18Rα) expressed in lung tissues of mice with allergic asthma (AM).Methods Healthy mice (HM) and AM alveolar lavage fluid (BALF) were collected and their lung tissues were prepared into single-cell suspensions, and the ratio of CD4 Th2 cells to Th17 cells and the expression level of IL-18Rα were detected by flow cytometry. Enzyme-linked immune sorbent assay (ELISA) was used to detect the levels of cytokines IL-4 and IL-17A in BALF.Results Compared with HM, the proportions of CD4 Th2 cells and Th17 cells in AM lung tissue were significantly increased, and the expression level of IL-18Rα in CD4 Th2 cells was increased (P<0.05), while the expression level of IL-18α in Th17 cells was not statistically different, and IL-4 and IL-17A in AM BALF were significantly higher than those in HM group, and this difference was correlated with the proportion of Th2 and Th17 cells.Conclusion IL-18 may be involved in the pathogenesis of allergic asthma by inducing the differentiation of CD4 T cells into Th2 cells and Th17 cells, and up-regulating the expression of IL-18Rα in Th2 cells in lung tissue of asthma mice.

研究目的：探讨白细胞介素18（interleukin 18, IL-18）对过敏性哮喘（allergic asthma, AM）小鼠肺组织中CD4辅助性T细胞2（Th2）、辅助性T细胞17（Th17）的分化及白细胞介素18受体α（IL-18Rα）表达水平的影响。
方法：收集健康小鼠（HM）及过敏性哮喘小鼠的肺泡灌洗液（bronchoalveolar lavage fluid, BALF），制备肺组织单细胞悬液，采用流式细胞术（flow cytometry）检测CD4+Th2细胞与Th17细胞的占比及IL-18Rα的表达水平；采用酶联免疫吸附试验（enzyme-linked immunosorbent assay, ELISA）检测肺泡灌洗液中细胞因子IL-4、IL-17A的水平。
结果：与健康小鼠组相比，过敏性哮喘小鼠肺组织中CD4+Th2细胞及Th17细胞的占比显著升高，CD4+Th2细胞中IL-18Rα的表达水平上调（P<0.05）；而Th17细胞中IL-18α的表达水平无统计学差异，且过敏性哮喘小鼠肺泡灌洗液中IL-4、IL-17A水平显著高于健康小鼠组，该差异与Th2、Th17细胞的占比呈相关性。
结论：IL-18可能通过诱导哮喘小鼠肺组织中CD4+T细胞向Th2、Th17细胞分化，并上调Th2细胞中IL-18Rα的表达，参与过敏性哮喘的发病过程。