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Abstract：
Allergic asthma (AA) is closely associated with the polarization of T helper (Th)2 and Th17 cells. Interleukin (IL)-18 acts as an inducer of Th2 and Th17 cell responses. However, expressions of IL-18 and IL-18 receptor alpha (IL-18Rα) in blood Th2 and Th17 cells of patients with AA remain unclear. We therefore investigated their expressions in Th2 and Th17 cells using flow cytometric analysis, quantitative real-time PCR (qPCR), and murine AA model. We observed increased proportions of Th2, Th17, IL-18+, IL-18+ Th2, and IL-18+ Th17 cells in blood CD4+ T cells of patients with AA. Additionally, house dust mite seemed to upregulate further IL-18 expression in Th2 and Th17, and upregulate IL-18Rα expression in CD4+ T, Th2, and Th17 cells of AA patients. It was also found that the plasma levels of IL-4, IL-17A, and IL-18 in AA patients were elevated, and they were correlated between each other. In ovalbumin (OVA)-induced asthma mouse (AM), we observed that the percentages of blood CD4+ T, Th2, and Th17 cells were increased. Moreover, OVA-induced AM expressed higher level of IL-18Rα in blood Th2 cells, which was downregulated by IL-18. Increased IL-18Rα expression was also observed in blood Th2 cells of OVA-induced FcεRIα-/- mice. Collectively, our findings suggest the involvement of Th2 cells in AA by expressing excessive IL-18 and IL-18Rα in response to allergen, and that IL-18 and IL-18Rα expressing Th2 cells are likely to be the potential targets for AA therapy.
摘要：
过敏性哮喘（AA）与T辅助细胞（Th）2和Th17细胞的极化密切相关。白细胞介素(IL)-18充当Th2和Th17细胞应答的诱导物。然而,AA患者血液Th2和Th17细胞中IL-18和IL-18受体α（IL-18Rα）的表达尚不清楚。因此，我们使用流式细胞术分析研究了它们在Th2和Th17细胞中的表达，qPCR和鼠AA模型。我们观察到Th2，Th17，IL-18+的比例增加，AA患者血CD4+T细胞中IL-18+Th2和IL-18+Th17细胞。此外,屋尘螨似乎进一步上调IL-18在Th2和Th17中的表达，并上调IL-18Rα在CD4+T中的表达，AA患者的Th2和Th17细胞。还发现AA患者的血浆IL-4，IL-17A和IL-18水平升高，它们之间是相互关联的。在OVA诱导的哮喘小鼠（AM）中，我们观察到血液CD4+T的百分比，Th2和Th17细胞增多。此外，OVA诱导的AM在血液Th2细胞中表达更高水平的IL-18Rα，它被IL-18下调。在OVA诱导的FcεRIα-/-小鼠的血液Th2细胞中也观察到IL-18Rα表达增加。总的来说，我们的发现提示Th2细胞参与AA通过表达过量的IL-18和IL-18Rα应答过敏原，表达IL-18和IL-18Rα的Th2细胞可能是AA治疗的潜在靶标。
