Potential role of Let-7 family microRNAs in sex disparity in asthma

<bold>Background:</bold> There are notable sex differences in the incidence, prevalence, and severity of asthma. Let-7 miRNAs were found to be decreased in asthma, but a possible role of Let-7 miRNAs in sex disparity in asthma is unknown. The Let-7 family was shown to regulate IL-13, an important cytokine produced by both innate and adaptive immune cells, which contributes to asthma pathogenesis. <bold>Aim:</bold> To examine whether Let-7 miRNAs play a role in sex disparity in asthma. <bold>Methods:</bold> Airway samples were collected from males and females with asthma. Let-7 miRNA expression in bronchial biopsies were determined by NanoString assay and qPCR. Type 2 innate lymphoid cells (ILC2s), T helper (Th)2 cells and IL-33 receptor (ST2L)+ cells from bronchial lavage (BL) were evaluated by flow cytometry. IL-13, thymic stromal lymphopoietin (TSLP), IL-33, and soluble IL-33R (sST2) were measured by ELISA in cell-free BL. <bold>Result:</bold> Let-7f, Let-7g and miR-98 expression in bronchial tissue tended to be higher in males compared to females (P=.0512, P=.0566 and P=.0579 respectively). In the BL, increased numbers of ILC2s were found in males compared to females (P=.0288) and ILC2s from males displayed higher expression of ST2L (P=.0320). In contrast, increased levels of IL-13 (P=.0007), TSLP (P<.0001), and sST2 (P=.0455) were found in females compared to males. <bold>Conclusion:</bold> Let-7 miRNAs may act as immune modulators in asthma by inhibiting the production of IL-13, resulting in reduced levels of IL-13 in males compared to females. Increased ST2L expression may promote the increased BL ILC2s observed in males. In contrast, increased sST2 in females may interfere with the chemoattractant function of IL-33 resulting in fewer BL ILC2s in females compared to males.