Micrococcus luteus-derived extracellular vesicles attenuate neutrophilic asthma by regulating miRNAs in airway epithelial cells

• Published in: Experimental & molecular medicine Vol. 55; no. 1; pp. 196 - 204
• Main Authors: Sim, Soyoon, Lee, Dong-Hyun, Kim, Kwang-sun, Park, Hyeon Ju, Kim, Yoon-Keun, Choi, Youngwoo, Park, Hae-Sim
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2023; Springer Nature B.V; 생화학분자생물학회
• Subjects: 45/61; 631/250/256/2515; 631/250/256/2516; 64/60; 82/79; 96/21; Animal models; Animals; Asthma; Bacteria; Bacterial vesicles; Biomedical and Life Sciences; Biomedicine; Bronchoalveolar Lavage Fluid; Bronchus; Cell activation; Disease Models, Animal; Epithelial cells; Epithelial Cells - metabolism; Extracellular vesicles; Extracellular Vesicles - metabolism; IL-1β; Immune response; Immunity, Innate; Immunoglobulin G; Inflammation; Interleukin 17; Lavage; Leukocytes (eosinophilic); Leukocytes (neutrophilic); Lung diseases; Lymphocytes - metabolism; Lymphoid cells; Medical Biochemistry; Membrane vesicles; Mice; Mice, Inbred C57BL; Micrococcus luteus; Micrococcus luteus - genetics; Micrococcus luteus - metabolism; MicroRNAs - metabolism; miRNA; Molecular Medicine; Monocytes; Patients; Respiratory tract; Respiratory tract diseases; Stem Cells; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-022-00910-0

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 FEV 1 (%) 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. Treatment of asthma using extracellular vesicles from bacteria Tiny membrane-bound sacs released by bacteria and containing a variety of biomolecules show potential as a novel treatment for asthma. These sacs, known as extracellular vesicles (EVs), are released by all living cells. Some bacterial EVs have been found to influence the immune response in animal models and asthmatic patients. Researchers in South Korea led by Youngwoo Choi and Hae-Sim Park at Ajou University School of Medicine, Suwon, demonstrated the beneficial effects of EVs from Micrococcus luteus bacteria on neutrophilic inflammation in patients with neutrophilic asthma. Studies in mice using cultured airway and immune systems cells revealed details of the mechanism of the EV’s effects. Bacterial EV biomolecules increased the production of regulatory RNA molecules, which inhibited cellular signaling pathways involved in neutrophilic asthma.