Sex differences in a murine model of asthma are time and tissue compartment dependent

Asthma is a sexually dimorphic disease with greater documented prevalence and severity in women compared to men. Immunological parameters in mouse models of asthma also exhibit sexual dimorphism, with female mice typically having higher Th2 inflammation than male mice. Despite the standard choice of ovalbumin (OVA) murine models of asthma to study sex differences, there is little consensus across different studies in model design, timelines of sample collection and measured endpoints. To seek agreement in previous reports, we sought to resolve the time course of unfolding sex differences in a standardized 6-challenge OVA murine model of asthma. Immune responses in both lung tissue and airway compartments were quantified by multi-color flow cytometry. OVA-specific immunoglobulin E (IgE) and IgG1 were assayed by ELISA. Several lung tissue markers showed sexual dimorphism as measured by quantitative PCR (qPCR), including cytokines IL-4, IL-5, IL-13 and IL-10 and repair markers nestin and tenascin C. Although females had greater responses in the late phase of the model, male-biased dimorphism was evident in early responses. While females had greater adaptive responses (T and B cells) and higher eosinophils, male data suggested a stronger innate immune response (monocytes, neutrophils). Females had significantly higher OVA-specific IgE prior to the elicitation phase of the model, indicating early sex differences during sensitization. The same parameters frequently had opposing patterns of dimorphism in lung tissue vs. airway. CONCLUSION: Sexual dimorphism in lung inflammation is both time and tissue compartment dependent. Spatiotemporal variability in sex differences in a murine model of asthma must be accounted for when planning experiments to model the sex bias in allergic inflammation.