Sex disparity in adult asthma: A potential immunomodulatory role of let-7 family microRNAs

Abstract

Background: Sex differences have been reported in the incidence, prevalence and severity of asthma. Previous findings from animal models have revealed sex-related differences in inflammatory pathways that may contribute to asthma pathogenesis, but human studies are limited. Methods: Airway and blood samples (n = 55 and n = 85 respectively) were collected from adult females and males with asthma and healthy subjects. Type 2 innate lymphoid cells (ILC2s), T helper (Th)2 cells and their expression of IL-33R/ST2 (ST2L) were evaluated by flow cytometry. IL-13, thymic stromal lymphopoietin (TSLP), IL-33 and soluble IL-33R/ST2 (sST2) were measured by ELISA. Let-7 miRNA expression in bronchial biopsies was determined by qPCR. Results: Females with asthma reported more exacerbations and had a higher number of airway eosinophils compared with males with asthma. Bronchial biopsy expression of Let-7f, Let-7g and miR-98 tended to be higher in males with asthma compared with females and inversely correlated with asthma exacerbations. In contrast, increased levels of IL-13, TSLP and sST2 were found in females with asthma compared with males. Conclusion: Our study demonstrates different inflammatory signatures between males and females with asthma. Let-7 miRNAs act as immune modulators by inhibiting the production of IL-13 and may be an important factor explaining the sex disparity seen in asthma.