Asthma is a common respiratory immune disease in children and adults, and interleukin-4 (IL-4) is one of the key factors for the onset of asthma. Therefore, targeting human IL-4 and IL-4 receptor alpha (IL-4RA) has become one of the strategies for targeted therapy of cytokines. Herein, we established an animal model of asthmatic airway inflammation using double humanized IL-4/IL-4RA (hIL-4/hIL-4RA) mice, where human IL-4 and IL-4RA replaced their murine counterparts, respectively. We successfully identified the phenotype by Southern blotting, ELISA, and flow cytometry. The hIL-4/hIL-4RA mice induced by ovalbumin (OVA) exhibited several important features of asthma, such as inflammatory cell infiltration, IgE release, goblet cell hyperplasia, and Th2 cytokine secretion. Furthermore, treatment of these humanized mice with anti-human IL-4RA antibodies significantly inhibited level of these pathological indicators. Thus, hIL-4/hIL-4RA mice provide a validated preclinical mouse model to interrogate new therapeutic agents targeting this specific cytokine pathway in asthma.

哮喘是儿童和成人常见的呼吸道免疫疾病，白细胞介素4（IL-4）是哮喘发作的关键因素之一。因此，靶向人IL-4和IL-4受体α（IL-4RA）已成为细胞因子靶向治疗的策略之一。在此，我们使用双重人源化 IL-4/IL-4RA（hIL-4/hIL-4RA）小鼠建立了哮喘气道炎症的动物模型，其中人 IL-4 和 IL-4RA 分别取代了它们的小鼠对应物。我们通过Southern印迹、ELISA和流式细胞术成功鉴定了表型。卵清蛋白（OVA）诱导的 hIL-4/hIL-4RA 小鼠表现出哮喘的几个重要特征，如炎症细胞浸润、IgE 释放、杯状细胞增生和 Th2 细胞因子分泌。此外，用抗人IL-4RA抗体处理这些人源化小鼠显着抑制了这些病理指标的水平。因此，hIL-4/hIL-4RA 小鼠提供了一种经过验证的临床前小鼠模型，以研究针对哮喘中这种特定细胞因子途径的新治疗剂。