Asthma affects millions of people around the world, but adult women are more likely than men to have the condition—and often experience more severe symptoms.
Many women also notice that their asthma changes during puberty, pregnancy, or menopause.
Until now, scientists have not fully understood why these sex-based differences occur.
A new study published in Science Immunology offers fresh clues. Researchers from Imperial College London’s National Heart and Lung Institute found that the female sex hormone estrogen may increase allergic inflammation in the lungs, potentially making asthma worse in females.
In the study, researchers exposed young male and female mice to house dust mite allergen, a common asthma trigger. They found that female mice developed a much stronger “type 2” immune response.
This type of inflammation is typically linked to allergic asthma. The female mice had higher levels of inflammatory signaling molecules and more airway inflammation compared to males.
These differences appeared after allergen exposure early in life, suggesting that biological sex and hormones may influence how the developing immune system responds to environmental triggers. The researchers wanted to understand what was driving this stronger inflammatory reaction in females.
They discovered that estrogen increased the production of a molecule called IL-33. This molecule plays a key role in activating immune cells involved in allergic inflammation. Higher IL-33 levels led to increased activity of a receptor called EGFR on certain immune cells known as T helper 2 (TH2) cells. These EGFR-positive cells then produced larger amounts of inflammatory substances that are associated with asthma symptoms.
When the researchers blocked EGFR signaling in female mice, the excessive type 2 inflammatory response was greatly reduced. In fact, the difference between males and females largely disappeared. The team also found that lung fibroblasts—structural cells that support the airways—were a major source of IL-33 during allergen exposure. Estrogen directly increased IL-33 release from these cells.
Although the findings are based on animal studies, they provide valuable insight into how hormones may shape immune responses in the lungs. This could help explain why asthma tends to be more severe in women and why symptoms can worsen during times of hormonal change.
The study also points to potential new treatment targets. The IL-33 and EGFR pathways may be especially important in people with “type 2-high” asthma, a form driven by allergic inflammation. Drugs that block IL-33 are already being tested in clinical trials, and better understanding who may benefit most could lead to more personalized treatments.
Researchers now plan to study whether similar hormone-related pathways operate in people with asthma.
By learning more about how sex hormones interact with immune and lung cells, scientists hope to develop better strategies to prevent asthma attacks and improve long-term outcomes, especially for women.
