Allergic asthma is a chronic inflammatory disorder associated with airway hyperreactivity (AHR) whose global prevalence is increasing at an alarming rate. Group 2 innate lymphoid cells (ILC2s) and T helper 2 (T_H2) cells are producers of type 2 cytokines, which may contribute to development of AHR. In this study, we explore the potential of CD52-targeted depletion of type 2 immune cells for treating allergic AHR. Here we show that anti-CD52 therapy can prevent and remarkably reverse established IL-33-induced AHR by reducing airway resistance and alleviating lung inflammation. We further show that CD52 depletion prevents and treats allergic AHR induced by clinically relevant allergens such as Alternaria alternata and house dust mite. Importantly, we leverage various humanized mice models of AHR to show new therapeutic applications for Alemtuzumab, an anti-CD52 depleting antibody that is currently FDA approved for treatment of multiple sclerosis. Our results demonstrate that CD52 depletion is a viable therapeutic option for reduction of pulmonary inflammation, abrogation of eosinophilia, improvement of lung function, and thus treatment of allergic AHR. Taken together, our data suggest that anti-CD52 depleting monoclonal antibodies, such as Alemtuzumab, can serve as viable therapeutic drugs for amelioration of T_H2- and ILC2-dependent AHR.

过敏性哮喘是一种与气道高反应性 (AHR) 相关的慢性炎症性疾病，其全球患病率正以惊人的速度增长。第 2 组先天性淋巴样细胞 (ILC2s) 和 T 辅助细胞 2 (T _H 2) 细胞是 2 型细胞因子的生产者，这可能有助于 AHR 的发展。在这项研究中，我们探索了 CD52 靶向耗竭 2 型免疫细胞治疗过敏性 AHR 的潜力。在这里，我们表明抗 CD52 疗法可以通过降低气道阻力和减轻肺部炎症来预防和显着逆转已建立的 IL-33 诱导的 AHR。我们进一步表明，CD52 耗竭可预防和治疗由临床相关过敏原（如链格孢）引起的过敏性 AHR和屋尘螨。重要的是，我们利用 AHR 的各种人源化小鼠模型来展示阿仑单抗的新治疗应用，阿仑单抗是一种抗 CD52 耗竭抗体，目前已获 FDA 批准用于治疗多发性硬化症。我们的结果表明，CD52 耗竭是一种可行的治疗选择，可用于减少肺部炎症、消除嗜酸性粒细胞增多、改善肺功能，从而治疗过敏性 AHR。总之，我们的数据表明，抗 CD52 耗竭单克隆抗体（例如阿仑单抗）可以作为改善 T _H 2 和 ILC2 依赖性 AHR 的可行治疗药物。