Vip+ vagal neurons control allergen-induced responses

Vagal sensory neurons innervating the lung control respiratory physiology and immunity, yet the subtypes mediating responses to specific inputs, i.e., allergen, remain undefined. Here, we identify Vip + and Tac1 + neurons as two vagal subsets with non-overlapping expression and divergent innervation profiles. Selective ablation of Vip + , but not Tac1 + , neurons leads to reduced airway hyperreactivity and type 2 cytokine expression, whereas chemogenetic activation of Vip + neurons leads to elevated responses. Bulk RNA sequencing of allergen-treated vagal ganglia reveals upregulation of Ngfr , the highly enriched receptor in Vip + vagal neurons. NGFR signaling is required for Vip + -mediated airway hyperreactivity. Furthermore, Vip + neurons project to the nucleus of the solitary tract (nTS) in the brainstem, and unilateral genetic ablation reduces FOS + activation in the ipsilateral nTS. These findings specify a vagal population that bridges peripheral allergen sensing and central output, revealing a neuroimmune mechanism along the body-brain axis that contributes to asthma.