Selective release of miRNAs via extracellular vesicles is associated with house-dust mite allergen-induced airway inflammation.
BACKGROUND
MicroRNAs (miRNAs) may facilitate cell-to-cell communication via extracellular vesicles (EVs). The biological roles of miRNAs in EVs on allergic airway inflammation are unclear.


METHODS
Airway-secreted EVs (AEVs) were isolated from bronchoalveolar lavage fluid (BALF) of control and house-dust mite (HDM) allergen-exposed HDM-sensitized mice. The expression of miRNAs in AEVs or miRNAs and mRNAs in lung tissue was analysed using miRNA microarray.


RESULTS
The amount of AEV increased 8.9-fold in BALF from HDM-exposed mice compared with that from sham-control mice. HDM exposure resulted in significant changes in the expression of 139 miRNAs in EVs and 175 miRNAs in lung tissues, with 54 miRNAs being common in both samples. Expression changes of these 54 miRNAs between miRNAs in AEVs and lung tissues after HDM exposure were inversely correlated. Computational analysis revealed that 31 genes, including IL-13 and IL-5Ra, are putative targets of the miRNAs up-regulated in AEVs but down-regulated in lung tissues after HDM exposure. The amount of AEV in BALF after HDM exposure was diminished by treatment with the sphingomyelinase inhibitor GW4869. The treatment with GW4869 also decreased Th2 cytokines and eosinophil counts in BALFs and reduced eosinophil accumulation in airway walls and mucosa.


CONCLUSION
These results indicate that selective sorting of miRNA including Th2 inhibitory miRNAs into AEVs and increase release to the airway after HDM exposure would be involved in the pathogenesis of allergic airway inflammation.
['Gon|Y|Y|http://orcid.org/0000-0003-0514-3054', 'Maruoka|S|S|', 'Inoue|T|T|', 'Kuroda|K|K|', 'Yamagishi|K|K|', 'Kozu|Y|Y|', 'Shikano|S|S|', 'Soda|K|K|', 'Lötvall|J|J|', 'Hashimoto|S|S|']
D000818:Animals D039741:Antigens, Dermatophagoides D001249:Asthma D001692:Biological Transport D001992:Bronchoalveolar Lavage Fluid D016207:Cytokines D004195:Disease Models, Animal D055354:Exosomes D000067128:Extracellular Vesicles D020869:Gene Expression Profiling D005786:Gene Expression Regulation D007249:Inflammation D008168:Lung D051379:Mice D035683:MicroRNAs D034622:RNA Interference D012333:RNA, Messenger D020545:Respiratory Mucosa D018418:Th2 Cells
miRNA extracellular vesicles house-dust mite Th2 immune response allergen asthma exosomes microvesicles