Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development

miRNAs are master regulators of signalling pathways critically involved in asthma and are transferred between cells in extracellular vesicles (EV). Researchers at the University of Groningen aimed to investigate if the miRNA content of EV secreted by primary normal human bronchial epithelial cells (NHBE) is altered upon asthma development.

NHBE cells were cultured at air-liquid interface and treated with Interleukin (IL)-13 to induce an asthma-like phenotype. EV isolations by precipitation from basal culture medium or apical surface wash were characterized by Nanoparticle Tracking Analysis, Transmission Electron Microscopy and Western Blot, and EV-associated miRNAs were identified by a RT-qPCR-based profiling. Significant candidates were confirmed in EVs isolated by size exclusion chromatography from nasal lavages of children with mild-to-moderate (n=8) or severe asthma (n=9), and healthy controls (n=9).

NHBE cells secrete EVs to the apical and basal side. 47 miRNAs were expressed in EVs and 16 thereof were significantly altered in basal EV upon IL-13 treatment. Expression of miRNAs could be confirmed in EVs from human nasal lavages. Of note, levels of miR-92b, miR-210 and miR-34a significantly correlated with lung function parameters in children (FEV1 FVC%pred and FEF25-75%pred ), thus lower EV-miRNA levels in nasal lavages associated with airway obstruction. Subsequent Ingenuity Pathway Analysis predicted the miRNAs to regulate Th2 polarization and dendritic cell maturation.

miR-92b,  miR-34a  and  miR-210  are  predicted  to  be  regulate  Th2 differentiation and dendritic cell maturation


IPA-predicted  network  of  miR-92b,  miR-34a,  and  miR-210  showing  predicted  targets  and their association with biological functions Th2 differentiation and dendritic cell maturation. Red indicates decrease on array, green indicates predicted increase.

These data indicate that secretion of miRNAs in EVs from the airway epithelium, in particular miR-34a, miR-92b and miR-210, might be involved in the early development of a Th2 response in the airways and asthma.

Bartel S, La Grutta S, Cilluffo G, Perconti G, Bongiovanni A, Giallongo A, Behrends J, Kruppa J, Hermann S, Chiang D, Pfaffl MW, Krauss-Etschmann S. (2019) Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development. Allergy [Epub ahead of print]. [abstract]

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