MiR-155-5p Differentially Regulates IL-13Rα1 and IL-13Rα2 Expression and Signalling, Driving Abnormal Lung Epithelial Cell Phenotype in Severe Asthma

MiR-155-5p is known to increase in innate and adaptive immune cells in response to IL-13 and is associated with asthma severity. However, little is known about its role in airway structural cells. BECs isolated from healthy donors and severe asthma patients were stimulated with IL-13. MiR-155-5p expression and release were measured by RT-PCR in BECs and in their derived exosomes. Modulation of miR-155-5p in BECs was performed using transfection of miR-155-5p inhibitor and mimic. IL-13Rα1, IL-13Rα2, MUC5AC, IL-8 and Eotaxin-1 expression were measured by RT-PCR and western blot. BECs repair process was assessed by wound healing assay. IL-13Rα1 and IL-13Rα2 expression and downstream pathways were evaluated by western blot. Dual Luciferase assay was used to determine miR-155-5p target genes associated to IL-13 receptors signaling. BECs from severe asthma showed an increased expression and exosomal release of miR-155-5p at baseline that was amplified by IL-13 stimulation. BECs from asthmatics expressed more IL-13Rα1 and less IL-13Rα2 than healthy donors and IL-13Rα1 but not IL-13Rα2 induced miR-155-5p expression under IL-13 stimulation. MiR-155-5p overexpression favored