In mice, male hormones strengthen nerves that curb asthma

The mice began receiving daily nasal doses of house dust mite extract at 15 days old, just as puberty started. After three weeks, both sexes had developed an allergic response, but the young males showed much less lung inflammation and fewer inflammatory immune cells than the females. The study, published in Science Immunology, identifies a possible reason: male hormones were helping build a protective nerve network in the lungs.

The result echoes a long-standing pattern observed in people. Asthma is more common in boys before puberty, then often improves in males while becoming more common and severe in females. In 2023, an estimated 363 million people worldwide had asthma and 442,000 died from it. To test the role of hormones, researchers removed the testicles in male mice and ovaries in female mice at 14 days old. Without natural hormones, the males lost their protection; testosterone injections calmed the inflammation again.

The lungs were not being protected by testosterone acting directly on immune cells. Instead, androgen receptors — proteins that respond to male sex hormones — on sympathetic nerves switched on genes involved in nerve growth and development. Male lungs then developed a denser, more highly branched supply of these nerves. They released norepinephrine, a neurotransmitter that acted as a brake on the immune proteins driving type 2 pulmonary inflammation.

The researchers tested that link with genetically engineered mice whose sympathetic nerves lacked androgen receptors. Their hormones were normal elsewhere, but their lung nerves grew poorly. After allergen exposure, the mice developed severe inflammation and heavy mucus in their airways. That result places the nerve connection, rather than hormone levels alone, at the center of the proposed mechanism.

So what changes, concretely? Not asthma treatment for people yet: the evidence comes from mice, and the researchers still need to establish whether humans share the pathway from childhood through puberty and adulthood. But the work offers clues about asthma’s changing course and potential new ways to kickstart remission.