Involvement of miRNA-17 and -21 in regulatory T cell (Treg) function in asthma

Background: Tregs have been shown to be functionally modulated in allergic asthma (Hartl et al., JACI, 2007; Raedler et al., JACI, 2015). Recently, we observed that microRNA (miR)-17, and miR-21 are increased in murine experimental asthma and transfection of primary murine CD4+ T cells with both miRNAs reduced Treg differentiation and function in vitro. Thus, we aimed to investigate if miR-17 and miR-21 are involved in Treg function in paediatric allergic asthma. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from 7 healthy control children (HC), 7 with allergic asthma (AA), and 7 with non-allergic asthma (NA) (Clinical Asthma Research Association cohort study (Raedler et al., JACI, 2015)) and stimulated with lipid A (LpA), anti-CD3/CD28 or none. Frequencies of Treg in blood were quantified via flow cytometry. microRNA were assessed by qRT-PCR. Results: miR-17 and miR-21 levels were significantly increased in PBMCs after stimulation with anti-CD3/CD28, but did not differ significantly among HCs, NA or AA overall. We observed a positive correlation of PBMC miR-17 (r=-0.519, p=0.023), and miR-21 (r=-0.519, p=0.023) expression with percentages of CD4+CD25+Foxp3+CD49d- T cells, while they were negatively correlated with CD4+IL17+ T cells (miR-17: r=0.555, p=0.014; miR-21: r=0.621, p= 0.005). miR-21 also negatively correlated with IL10 levels in AA (r=0.886, p=0.033). Conclusion: miRNA levels in PBMCs seem to be influenced by different stimulations and their expression correlates with distinct cell types and cytokines in the blood. A dysregulation of miRNAs during the development of allergic asthma may thus contribute to the development of chronic airway inflammation.