Department of Critical Care Medicine, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, Henan, China.
Department of Respiration, Huaihe Hospital of Henan University, Kaifeng, Henan, China.
Clin Exp Immunol. 2024 Jun 20;217(1):31-44. doi: 10.1093/cei/uxae022.
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.
变应性哮喘（AA）与辅助性 T 细胞（Th）2 和 Th17 细胞的极化密切相关。白细胞介素（IL）-18 作为 Th2 和 Th17 细胞反应的诱导剂。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、实时定量 PCR（qPCR）和 AA 小鼠模型来研究它们在 Th2 和 Th17 细胞中的表达。我们观察到 AA 患者血液 CD4+T 细胞中 Th2、Th17、IL-18+、IL-18+Th2 和 IL-18+Th17 细胞的比例增加。此外，屋尘螨似乎进一步上调了 Th2 和 Th17 中的 IL-18 表达，并上调了 AA 患者 CD4+T、Th2 和 Th17 细胞中的 IL-18Rα 表达。还发现 AA 患者的血浆 IL-4、IL-17A 和 IL-18 水平升高，且相互之间呈正相关。在卵清蛋白（OVA）诱导的哮喘小鼠（AM）中，我们观察到血液 CD4+T、Th2 和 Th17 细胞的比例增加。此外，OVA 诱导的 AM 在血液 Th2 细胞中表达更高水平的 IL-18Rα，而 IL-18 则下调了该水平。OVA 诱导的 FcεRIα-/-小鼠的血液 Th2 细胞中也观察到 IL-18Rα表达增加。综上所述，我们的研究结果表明，过敏原刺激下 Th2 细胞通过过度表达 IL-18 和 IL-18Rα 参与 AA 的发病机制，表达 IL-18 和 IL-18Rα 的 Th2 细胞可能是 AA 治疗的潜在靶点。
