No 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