Gender specific increase of IL-17A in a murine model of asthma in the absence of T-bet (163.8)

Abstract

Abstract Recent studies in humans have suggested that females may be more susceptible to allergic asthma than male. In addition, studies in Balb/c mice revealed that females have higher serum IgE levels, Th2 cytokines and an increased number of CD4+ T-cells. Mice lacking the Th1-specific transcriptional factor T-bet (T-bet-/-) show a severe phenotype of asthma with increased AHR, eosinophils and Th2 type cytokines in their airways. We therefore analyzed gender specific immune-responses in T-bet-/- mice in a murine model of allergic asthma. To this aim, we first looked at the Th2 inducing cytokine IL-6 and found it induced in the airways of naïve T-bet-/- mice. IL-6 inhibits T regulatory cells and together with TGFβ1 induces Th17 cells. We then studied the expression of different cytokines involved in the development of the Th17-pathway in a gender dependent manner. We found that total lung cells isolated from asthmatic female T-bet-/- mice release increased levels of IL-6, TGFβ1 and IL-17 compared to the male littermates. Consistently, in these mice, other cytokines of the Th17-pathway like IL-23 and IL-21 were also found induced in the lung of female T-bet-/- mice as compared to the levels measured in the lung of males. These results might explain why females are more susceptible than males to some aspects of asthma and therefore gender specific studies in asthma might help to better design therapies for this disease.