A new study published in Science Immunology by researchers at the University of Zhejiang offers a biological explanation for why adolescent females experience asthma at higher rates than males. According to the research team led by Jing Yang, male sex hormones such as testosterone promote the development of sympathetic nerve fibers in lung tissue, which helps suppress allergic inflammation through the release of noradrenaline.
The Shift in Asthma Rates Between Childhood and Adolescence
Asthma is a chronic pulmonary disease that inflames, narrows, and produces mucus in the airways, making breathing difficult. Epidemiological patterns show a distinct shift during development: during childhood, boys are more commonly affected by the condition than girls. However, this dynamic changes during puberty, after which asthma becomes more prevalent among females.
To investigate this biological pivot, researchers at the University of Zhejiang conducted experiments using murine models exposed to house dust mites, a standard allergen utilized to simulate allergic asthma responses in laboratory settings. According to the study findings, female mice developed a significantly more intense type 2 inflammatory response than males.
How Androgens Regulate Pulmonary Immunity
The research team discovered that endogenous androgen production in male mice mitigated type 2 pulmonary inflammation following repeated allergen exposure in early life. When investigators surgically removed the gonads of the male mice prior to allergen exposure, the physiological differences in inflammation between the sexes disappeared.
Furthermore, when researchers administered testosterone to the gonadectomized mice, the treatment successfully reduced both immune cell infiltration and the production of inflammatory molecules. The data indicated that androgens influence more than just immune cells; they also act directly on lung cells that express androgen receptors—the specific proteins required to respond to male sex hormones.
According to the published findings, male mice with intact sex hormones maintained a higher density of sympathetic nerve fibers in their lung tissue compared to animals that underwent gonadectomy. Testosterone promoted the expansion of a neural network capable of communicating directly with the immune system.
The underlying mechanism relies on noradrenaline. Sympathetic nerve fibers within the lungs release this neurotransmitter, and local immune cells—specifically type 2 innate lymphoid cells (ILC2)—possess receptors capable of responding to it. Experiments demonstrated that noradrenaline reduces the production of IL-5, a cytokine that drives eosinophil accumulation in the airways.
Study Limitations and Future Implications
Despite these clear mechanistic insights in animal models, the study authors emphasize that testosterone cannot currently be used as a therapeutic treatment for human asthma patients. Administering sex hormones produces widespread systemic effects across numerous tissues throughout the body, meaning these findings represent a foundational step in understanding cellular pathways rather than an immediate clinical intervention.
Researchers also note that male hormones are not the sole factor governing airway inflammation, as female sex hormones likewise modify immune responses and respiratory function. Additional clinical research is required to determine whether this precise neuro-immune communication circuit functions identically in human patients.
Worth a look