We first demonstrated that miR-146a-3p suppressed Th17 differentiation by targeting MBD2 in severe asthma and miR-146a-3p overexpression significantly reduced airway hyperresponsiveness, airway inflammation and airway mucus secretion and inhibited the Th17 cells response, which suppressed the development of severe asthma, providing a potential novel therapeutic for Th17 predominant neutrophilic severe asthma. This evidence concerns the gene MBD2 and airway hyperresponsiveness.