Lung-innervating neurons expressing TMC3 control broncho-constriction and dilation with direct impact on lung tidal volume (RNA-Seq)

Sensory neurons of the vagal ganglia (VG) innervate lungs and play a critical role in maintaining airway homeostasis. However, specific VG neurons that innervate lungs, and mechanisms by which these neurons sense and respond to airway insults, are not well understood. Here, we identify a subpopulation of lung-innervating VG neurons defined by their expression of TMC3. Single cell transcriptomics illuminated several subpopulations of TMC3+ VGs afferents, revealing distinct Piezo2 and Trpv1-expressing subclusters. Furthermore, TMC3 deficiency in VG neurons leads to global and subcluster specific transcriptional changes involved in metabolic and ion channel function. Importantly, we show that broncho-constriction and dilation can be modulated through inhibition or activation of TMC3+ VG neurons with a direct impact on lung tidal volume. Together, our data show that TMC3 is a marker of specific lung-innervating neurons and may play a pivotal role in maintaining fundamental inspiratory and expiratory processes.