In the “battle of the sexes,” physiology often favors females, especially when it pertains to a hormone like testosterone. Yet now, a group of Australian researchers at the Walter and Eliza Hall Institute (WEHI) believe that the androgen molecule may protect males against developing asthma and be the underlying reason why females are two times more likely to develop the lung disorder after puberty. Findings from the current study—published online today in the Journal of Experimental Medicine in an article entitled “Androgen Signaling Negatively Controls Group 2 Innate Lymphoid Cells”—showed that testosterone suppresses the production of a type of immune cell that triggers allergic asthma. The finding may lead to new, more targeted asthma treatments.
One in nine Australians (2.5 million people) and roughly one in 12 Americans (25 million) have asthma, which is classified as an inflammatory airway condition. During an asthma attack, the airways swell and narrow, making it difficult to breathe. In adults, asthma is two times more prevalent and more severe in women than men, despite more being more common in boys than girls before puberty.
Interestingly, in 2016 the city of Melbourne, Australia, experienced a “thunderstorm asthma” event that was unprecedented internationally in its scale and severity of consequences, with almost 10,000 people visiting hospitals over a 2-day period. Thunderstorm asthma refers to allergic asthma thought to be initiated by an allergy to grass pollen. Many people with no history of asthma experienced severe asthma attacks. For years, researchers have speculated that hormones play a significant role in the incidence and severity of asthma in women.
[The Walter and Eliza Hall Institute]
“There is a very interesting clinical observation that women are more affected and develop more severe asthma than men, and so we tried to understand why this was happening,” explained lead study investigator Cyril Seillet, Ph.D., a senior research scientist at WEHI. “Our research shows that high levels of testosterone in males protect them against the development of allergic asthma. We identified that testosterone is a potent inhibitor of innate lymphoid cells, a newly described immune cell that has been associated with the initiation of asthma.”
The investigators found that innate lymphoid cells—or ILC2s— were able to sense testosterone levels and responded by halting production of the cells. ILC2s are found in the lungs, skin, and other organs. These cells produce inflammatory proteins that can cause lung inflammation and damage in response to common triggers for allergic asthma, such as pollen, dust mites, cigarette smoke, and pet hair.
“Testosterone directly acts on ILC2s by inhibiting their proliferation,” Dr. Seillet noted. “So, in males, you have less ILC2s in the lungs, and this directly correlates with the reduced severity of asthma.”
The research team is optimistic that their new findings will lead to a greater understanding of the mechanism that drives the sex differences in allergic asthma—ultimately leading to new treatments for the disease.
“Current treatments for severe asthma, such as steroids, are very broad based and can have significant side effects,” concluded study co-author Gabrielle Belz, Ph.D., D.V.Sc., professor and laboratory head at WEHI. “This discovery provides us with a potential new way of treating asthma, by targeting the cells that are directly contributing to the development of allergic asthma. While more research needs to be done, it does open up the possibility of mimicking this hormonal regulation of ILC2 populations as a way of treating or preventing asthma. Similar tactics for targeting hormonal pathways have successfully been used for treating other diseases, such as breast cancer.”