Estrogen affect the immune system and leads to more severe asthma in females

Introduction/Aim: Women have a higher incidence of asthma compared to men and exacerbations in women are often more severe and correlate with high estrogen levels. Using an experimental animal model for asthma, we have observed that female rats with experimental asthma also develop more severe exacerbations compared to male rats. The aim of the study was to investigate if the female sex hormone estrogen can impact the asthma response and identify the immunological mechanism for this effect. Methods: By implanting estrogen-releasing pellets into male rats prior to ovalbumin-sensitisation and re-challenge we investigated how estrogen-exposed males responded compared to untreated males and females. We used multi parameter flow cytometry to investigate proportion and activation of antigen presenting dendritic cells, responding T effector and regulatory T cells in airways before and after allergen rechallenge. Results: We discovered that estrogen was sufficient to induce a female-like disease phenotype during exacerbations in male rats. Interestingly, male and female rats also displayed significant differences in CD4 +/CD8+ T cell ratios in airway draining lymph nodes and this was directly impacted by estrogen exposure. In addition, female and estrogen treated male rats, but not male rats, displayed signs of recruitment of CD4+ cells into the airways following allergen re-challenge which most likely contributed to the exacerbated response. Conclusion: Our data suggest that estrogen is sufficient to induce female like asthma symptoms in male rats and appears to alter the T cell balance promoting allergic responses. Grant Support: The study was funded by the Asthma Foundation of Western Australia, the Telethon Kids Institute and the Swedish Society for Medical Research