Unraveling the role of miR-223-3p in the regulation of airway inflammation in asthma and COPD

miR-223-3p expression has been associated with inflammation in lung disease. We aimed to confirm previous findings on miR-223-3p expression and its association with neutrophilia as well as eosinophilia in an independent asthma and COPD cohort. Additionally, we investigated the effect of miR-223-3p on pro-inflammatory activity of airway epithelial cells (AEC) using asthma and COPD-related triggers. MiR-223-3p expression was assessed in bronchial biopsies of asthma patients (n=46) and healthy controls (n=82) using RNA-sequencing and in lung tissue of ex-smoking COPD patients (n=15) and ex-smoking controls (n=18 ) using qPCR. Primary AEC from healthy donors were transfected with miR-223-3p, treated with house dust mite (HDM), cigarette smoke extract (CSE) or viral mimic poly-(I:C) and secretion of GM-CSF and CXCL8 was measured using ELISA. Bronchial biopsies from asthmatics displayed significantly higher miR-223-3p levels compared to controls, with a positive correlation between miR-223-3p and eosinophils. COPD patients had significantly higher miR-223-3p levels in their lung tissue compared to ex-smoking controls, with a positive correlation between miR-223-3p and neutrophils. In AEC, miR-223-3p was hardly detectable. Overexpression of miR-223-3p significantly reduced GM-CSF and CXCL8 levels at baseline and upon HDM, CSE or poly-(I:C) stimulation. Higher levels of miR-223-3p in asthma and COPD patients are associated with eosinophilia and neutrophilia. Our in vitro data suggest that miR-223-3p acts as an anti-inflammatory miRNA to control airway epithelial activity. Ongoing studies are being performed to asses if this regulatory mechanism is disturbed in diseased epithelium.