Research findings evermore suggest a crucial role of myeloid-derived suppressor cells (MDSCs) in chronic lung diseases including asthma. Previously, we showed that intravenous (IV) treatment with a prostaglandin E2 receptor 4 (EP4) agonist, L-902,688, promoted MDSC suppressive activity. IV therapy with L-902,688 and BCT-100, a human pegylated arginase-1, ameliorated lung inflammatory features in a murine model of asthma. Here, we further investigate the potential therapeutic approach by studying the local therapy effects on the lungs after intranasal (IN) application. Using a two-week model of house dust mite (HDM)-induced murine asthma, the effect of IN treatment with L-902,688 or BCT-100 on in vivo lung function, inflammatory features of asthma and MDSC generation and activation was studied. Our experiments demonstrated increased suppressive activity of pulmonary MDSCs after induction of allergic airway disease. IN treatment with L-902,688 and BCT-100 further enhanced the immunosuppressive activity of pulmonary MDSCs. Additionally, treatment with BCT-100 reduced pulmonary T cell numbers. Asthmatic mice that received IN L-902,688 showed improved in vivo lung function. In conclusion, our results underline the potential of modulating MDSCs systemically or locally as a future therapeutic option in airway inflammatory diseases such as asthma.

研究结果不断表明，骨髓源性抑制细胞 (MDSC) 在包括哮喘在内的慢性肺部疾病中发挥着至关重要的作用。此前，我们发现前列腺素 E2 受体 4 (EP4) 激动剂 L-902,688 静脉注射 (IV) 治疗可促进 MDSC 抑制活性。使用 L-902,688 和 BCT-100（一种人聚乙二醇化精氨酸酶 1）进行静脉注射治疗可改善小鼠哮喘模型中的肺部炎症特征。在这里，我们通过研究鼻内（IN）应用后对肺部的局部治疗效果来进一步研究潜在的治疗方法。使用为期两周的屋尘螨 (HDM) 诱导的小鼠哮喘模型，研究了用 L-902,688 或 BCT-100 进行 IN 治疗对体内肺功能、哮喘炎症特征以及 MDSC 生成和激活的影响。我们的实验表明，诱导过敏性气道疾病后，肺部 MDSC 的抑制活性增加。L-902,688 和 BCT-100 的 IN 治疗进一步增强了肺 MDSC 的免疫抑制活性。此外，BCT-100 治疗减少了肺部T 细胞数量。接受 IN L-902,688 治疗的哮喘小鼠表现出体内肺功能的改善。总之，我们的结果强调了系统或局部调节 MDSC 作为哮喘等气道炎症性疾病未来治疗选择的潜力。