Bacterial extracellular vesicles (EVs) have been shown to regulate various pulmonary diseases, but their functions in asthma remain uncertain. To demonstrate the clinical significance of Micrococcus luteus-derived EVs (MlEVs) in asthma, we enrolled 45 asthmatic patients (20 patients with neutrophilic asthma [NA], 25 patients with eosinophilic asthma [EA]) and 40 healthy controls (HCs). When the prevalence of IgG1 and IgG4 specific to MlEVs was evaluated in serum by ELISA, lower levels of MlEV-specific IgG4 (but not IgG1) were noted in asthmatic patients than in HCs. Among asthmatic patients, significantly lower levels of MIEV-specific IgG4 were noted in patients with NA than in those with EA. Moreover, there was a positive correlation between serum MlEV-specific IgG4 levels and FEV₁ (%) values. In asthmatic C57BL/6 mice, MlEVs significantly attenuated neutrophilic airway inflammation by reducing the production of IL-1β and IL-17 in bronchoalveolar lavage fluid as well as the number of group 3 innate lymphoid cells (ILC3s) in lung tissues. To clarify the functional mechanism of MlEVs in NA, the effect of MlEVs on airway epithelial cells (AECs) and immune cells was investigated ex vivo. According to microarray analysis, MlEVs upregulated hsa-miR-4517 expression in AECs. Moreover, this miRNA could suppress IL-1β production by monocytes, resulting in the inhibition of ILC3 activation and neutrophil recruitment. These findings suggest that MlEVs could be a novel therapeutic agent for managing unresolved NA by regulating miRNA expression in AECs.

细菌细胞外囊泡 (EV) 已被证明可以调节各种肺部疾病，但它们在哮喘中的功能仍不确定。为了证明藤黄微球菌衍生的 EV (MlEV) 在哮喘中的临床意义，我们招募了 45 名哮喘患者（20 名中性粒细胞性哮喘 [NA] 患者、25 名嗜酸性粒细胞性哮喘 [EA] 患者）和 40 名健康对照者 (HC) 。当通过 ELISA 评估血清中 MlEV 特异性 IgG1 和 IgG4 的流行率时，发现哮喘患者中的 MlEV 特异性 IgG4（但不是 IgG1）水平低于 HC。在哮喘患者中，NA 患者的 MIEV 特异性 IgG4 水平显着低于 EA 患者。_{此外，血清 MlEV 特异性 IgG4 水平与 FEV 1}呈正相关(%) 值。在哮喘 C57BL/6 小鼠中，MlEVs 通过减少支气管肺泡灌洗液中 IL-1β 和 IL-17 的产生以及肺组织中第 3 组先天性淋巴样细胞 (ILC3s) 的数量，显着减轻中性粒细胞气道炎症。为了阐明 MlEV 在 NA 中的功能机制，离体研究了 MlEV 对气道上皮细胞 (AEC) 和免疫细胞的影响。根据微阵列分析，MlEV 上调了 AEC 中的 hsa-miR-4517 表达。此外，这种 miRNA 可以抑制单核细胞产生 IL-1β，从而抑制 ILC3 激活和中性粒细胞募集。这些发现表明，MlEV 可能是一种新型治疗剂，可通过调节 AEC 中的 miRNA 表达来管理未解决的 NA。