Sex‐based differences in CD103+ dendritic cells promote female‐predominant Th2 cytokine production during allergic asthma

Abstract

Gender disparities in adult patients with asthma regarding its prevalence and severity are mainly due to enhanced type 2 T-helper (Th2) cytokine production in female patients compared to that in male patients. However, the pathways mediating this effect remain unclear. We aimed to determine the roles of two major subsets of dendritic cells (DCs) in females, specifically those displaying CD11b or CD103, during enhanced Th2 priming after allergen exposure, using an ovalbumin-induced asthma mouse model. Sex-based differences in the number of DCs at inflamed sites, costimulatory molecule expression on DCs, and the ability of DCs to differentiate naïve CD4+ T cells into Th2 population were evaluated after allergen exposure in asthmatic mice. In addition, we assessed the role of 17β-oestradiol in CD103+ DC function during Th2 priming invitro. The number of CD11bhigh DCs and CD103+ DCs in the lung and bronchial lymph node (BLN) was increased to a greater extent in female mice than in male mice at 16 to 20hours after ovalbumin (OVA) inhalation. In BLNs, CD86 and I-A/I-E expression levels and antigen uptake ability in CD103+ DCs, but not in CD11bhigh DCs, were greater in female mice than in male mice. Furthermore, CD4+ T cells cultured with CD103+ DCs from female mice produced higher levels of interleukin (IL)-4, IL-5, and IL-13, compared with CD4+ T cells cultured with CD103+ DCs from male mice. The 17β-oestradiol-oriented enhancement of CD86 expression on CD103+ DCs after allergen exposure induced the enhanced IL-5 production from CD4+ T cells. These findings suggest that with regard to asthma, enhanced Th2 cytokine production in females might be attributed to 17β-oestradiol-mediated Th2-oriented CD103+ DCs in the BLN.