PMID- 36639716
OWN - NLM
STAT- MEDLINE
DCOM- 20230207
LR  - 20230217
IS  - 2092-6413 (Electronic)
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 55
IP  - 1
DP  - 2023 Jan
TI  - Micrococcus luteus-derived extracellular vesicles attenuate neutrophilic asthma 
      by regulating miRNAs in airway epithelial cells.
PG  - 196-204
LID - 10.1038/s12276-022-00910-0 [doi]
AB  - 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-1beta 
      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-1beta 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.
CI  - (c) 2023. The Author(s).
FAU - Sim, Soyoon
AU  - Sim S
AD  - Department of Allergy and Clinical Immunology, Ajou University School of 
      Medicine, Suwon, Korea.
AD  - Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, 
      Korea.
FAU - Lee, Dong-Hyun
AU  - Lee DH
AD  - Department of Allergy and Clinical Immunology, Ajou University School of 
      Medicine, Suwon, Korea.
AD  - Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, 
      Korea.
FAU - Kim, Kwang-Sun
AU  - Kim KS
AUID- ORCID: 0000-0003-3703-5461
AD  - Department of Chemistry and Chemistry Institute for Functional Materials, Pusan 
      National University, Busan, Korea.
FAU - Park, Hyeon Ju
AU  - Park HJ
AD  - MD Healthcare Inc., Seoul, Korea.
FAU - Kim, Yoon-Keun
AU  - Kim YK
AD  - MD Healthcare Inc., Seoul, Korea.
FAU - Choi, Youngwoo
AU  - Choi Y
AD  - Department of Allergy and Clinical Immunology, Ajou University School of 
      Medicine, Suwon, Korea. cyw3789@gmail.com.
FAU - Park, Hae-Sim
AU  - Park HS
AUID- ORCID: 0000-0003-2614-0303
AD  - Department of Allergy and Clinical Immunology, Ajou University School of 
      Medicine, Suwon, Korea. hspark@ajou.ac.kr.
AD  - Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, 
      Korea. hspark@ajou.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230113
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *MicroRNAs/metabolism
MH  - Micrococcus luteus/genetics/metabolism
MH  - Immunity, Innate
MH  - Mice, Inbred C57BL
MH  - Lymphocytes/metabolism
MH  - *Asthma
MH  - Bronchoalveolar Lavage Fluid
MH  - Epithelial Cells/metabolism
MH  - *Extracellular Vesicles/metabolism
MH  - Disease Models, Animal
PMC - PMC9898544
COIS- The authors declare no competing interests.
EDAT- 2023/01/14 06:00
MHDA- 2023/02/08 06:00
PMCR- 2023/01/13
CRDT- 2023/01/13 23:36
PHST- 2022/05/24 00:00 [received]
PHST- 2022/11/15 00:00 [accepted]
PHST- 2022/11/10 00:00 [revised]
PHST- 2023/01/14 06:00 [pubmed]
PHST- 2023/02/08 06:00 [medline]
PHST- 2023/01/13 23:36 [entrez]
PHST- 2023/01/13 00:00 [pmc-release]
AID - 10.1038/s12276-022-00910-0 [pii]
AID - 910 [pii]
AID - 10.1038/s12276-022-00910-0 [doi]
PST - ppublish
SO  - Exp Mol Med. 2023 Jan;55(1):196-204. doi: 10.1038/s12276-022-00910-0. Epub 2023 
      Jan 13.