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.