Androgen signaling via sympathetic neurons regulates allergic pulmonary inflammation

Sex differences in rates of asthma onset and remission suggest that core pathological mechanisms are modulated by gonadal hormones. Here we demonstrate in mice that surging androgen production is primarily responsible for suppressing pulmonary type 2 inflammation following repeated allergen exposures during early life. Whereas immune cells are known to respond to androgen signaling, we show that androgens also regulate peripheral sympathetic neurons to promote pulmonary innervation. Ablation of androgen receptors in sympathetic neurons disturbed allergen-induced pulmonary immunity and amplified type 2 inflammatory responses. Together, our findings reveal an endocrine-neuro-immune axis that serves to augment the progression of allergic asthma during development.