Unravelling the role of miR-223 in the regulation of pollutant-aggravated allergic airway inflammation

Abstract

Since miR-223 is highly expressed in neutrophils and eosinophils, we investigated its role in regulating allergic airway inflammation.

MiR-223-3p expression was determined in biopsies from eosinophilic, neutrophilic and paucigranulocytic asthma patients and healthy controls. GM-CSF release was studied in 16HBE and primary airway epithelial cells (AECs) transfected with miR-223-3p mimics. Pulmonary inflammatory responses and gene expression profiles were studied in wild type (WT) and miR-223 deficient mice exposed to saline, diesel exhaust particles (DEP), house dust mite (HDM), or combined HDM+DEP.

MiR-223-3p levels were higher in biopsies of eosinophilic asthma patients and in lungs of HDM+DEP-exposed mice. MiR-223-3p mimic in 16HBE and AECs reduced GM-CSF secretion. DEP aggravated the pulmonary inflammatory response towards HDM in WT mice. In HDM+DEP exposed miR-223 deficient mice, this response was significantly reduced in bronchoalveolar lavage (BAL), but not in lung. Upon sole HDM exposure, miR-223 deficiency did not affect BAL inflammation, but it increased peribronchial eosinophilic inflammation, goblet cell hyperplasia and IL-5 and IL-13 secretion, which was accompanied by upregulation of genes involved in eosinophil recruitment/activation, inflammation and chemotaxis.

In conclusion, miR-223 expression in asthma may suppress type 2 airway inflammation by impacting on GM-CSF, eosinophil function and goblet cell hyperplasia, but may not be sufficient to suppress severe pollutant-aggravated inflammation.

Funding: U4 funding UGent/UMCG (05U40516), UGent BOF/GOA01G00819, FWO Flanders (3G041819, G052518N, EOS G0G2318N). Chiesi Chair on Environmental factors in Asthma.