Th17 (T-helper 17) cells subtype of non-T2 (non-type 2)
asthma is related to neutrophilic infiltration and resistance to inhaled
corticosteroids (ICS), so is also known as severe
asthma. Methyl-CpG binding domain
protein 2 (MBD2) regulates the differentiation of the Th17 cells, tending to show a therapeutic target in severe
asthma. miR-146a-3p is associated with anti-inflammatory characteristics and immunity. Moreover, bioinformatic analysis showed that MBD2 may be a target gene of miR-146a-3p. However, the role of miR-146a-3p in the differentiation of Th17 cells via MBD2 in severe
asthma remains unknown. Here, we aimed to explore how miR-146a-3p interacts with MBD2 and affects the differentiation of Th17 cells in severe
asthma. First, we recruited 30 eligible healthy people and 30 patients with severe
asthma to detect the expression of miR-146a-3p in peripheral blood mononuclear cells (PBMCs) by qRT-PCR. Then, we established a HDM/LPS (house dust mite/
lipopolysaccharide) exposure model of bronchial epithelial cells (BECs) to evaluate the expression of miR-146a-3p, the interaction between miR-146a-3p and MBD2 using western blot and
luciferase reporter analysis and the effect of miR-146a-3p regulated Th17 cells differentiation by flow cytometry in BECs in vitro. Finally, we constructed a mouse model of Th17 predominant neutrophilic severe
asthma to assess the therapeutic potential of miR-146a-3p in severe
asthma and the effect of miR-146a-3p regulated Th17 cells differentiation via MBD2 in vivo. Decreased miR-146a-3p expression was noted in severe
asthma patients, in the BECs and in the animal severe
asthma models. Moreover, we demonstrated that miR-146a-3p suppressed Th17 cells differentiation by targeting the MBD2. miR-146a-3p overexpression significantly reduced
airway hyperresponsiveness, airway
inflammation and airway mucus secretion, while also inhibiting Th17 cells response in vivo, which relieved severe
asthma. By targeting MBD2 to suppress Th17 cells differentiation, miR-146a-3p provides a potential novel therapeutic for Th17 predominant neutrophilic severe
asthma.