Sensory neurons shape allergic Type 2 inflammation in the sinonasal tract

Abstract

Abstract Whether neuro-immune interactions regulate homeostasis vs. inflammation within the sinonasal tract is entirely unknown. Transient receptor potential vanilloid 1 ion channel (TRPV1+)-expressing sensory neurons of the trigeminal ganglion (TG) innervate the upper airway near sinonasal tuft cells (STC), a rare lineage of epithelial cells that initiate inflammation in the intestine by secreting pro-Type 2 cytokines. Given the vicinity of STC and TG neurons, we hypothesized that STC function(s) may be at least partially controlled by neuronal inputs. A mouse model of sinonasal allergic inflammation was developed using intranasal administration of a fungal allergen mix (FAM) that mimics key aspects of chronic rhinosinusitis pathophysiology, including increased numbers of sneezing bouts, STC, eosinophils, and levels of interleukin (IL)-25 in the sinonasal fluid. Our data show that FAM also evokes the release of neuropeptides substance P and neuromedin U from TG neurons. Also, chemical ablation of TRPV1+ neurons significantly reduces STC expansion and eosinophil accumulation, which collectively suggests that TRPV1+ sensory neurons produce factors that promote STC to release Type 2 cytokines driving allergic disease pathophysiology. Ongoing studies are designed to uncover important insight(s) into how STC/sensory neuron interactions are involved in the pathogenesis of allergic diseases in the sinonasal tract. Supported by grants from NIH (U01 AI163062, R01 AI164715, and R01 AI123173) awarded to DRH.