Allergen-induced dendritic cell migration is controlled through Substance P release by sensory neurons

Abstract

Dendritic cells (DCs) of the cDC2 lineage are necessary for the initiation of the allergic immune response and in the dermis are marked by their expression of CD301b.CD301b + dermal DCs respond to allergens encountered in vivo, but not in vitro. This suggests that another cell in the dermis may sense allergens and relay that information 5 to activate and induce the migration of CD301b + DCs to the draining lymph node. Using a model of cutaneous allergen exposure, we show that allergens directly activate TRPV1 + sensory neurons leading to itch and pain behaviors. Allergen-activated sensory neurons release the neuropeptide Substance P, which stimulates proximally located CD301b + DCs through MRGPRA1. Substance P induces CD301b + DC migration to the 10 draining lymph node where they initiate Th2 differentiation. Thus, sensory neurons act as primary sensors of allergens, linking exposure to activation of allergic-skewing DCs and the initiation of the allergic immune response. 15

Transient tear hyperosmolarity disrupts the neuroimmune homeostasis of the ocular surface and facilitates dry eye onset

“…endings in the skin detect allergen through their TRPV1 receptors and, by releasing substance P, recruit DCs. 58 Also, there is evidence of direct neurotoxicity induced by hyperosmolar tears on corneal nerve morphology and electrophysiological responses in rats. 59 The effect is detectable within minutes of continuous exposure of the ocular surface to hyperosmolar solutions, causing degeneration of sub-basal nerve fibres after several hours but no changes in intraepithelial nerve terminals.…”