한빛사논문
Soyoon Sim1,2, Dong-Hyun Lee1,2, Kwang-sun Kim3, Hyeon Ju Park4, Yoon-Keun Kim4, Youngwoo Choi1,5 and Hae-Sim Park1,2,5
1Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
2Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, Korea.
3Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan, Korea.
4MD Healthcare Inc., Seoul, Korea.
5These authors contributed equally: Youngwoo Choi, Hae-Sim Park
Corresponding authors: Correspondence to Youngwoo Choi or Hae-Sim Park.
Abstract
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.
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