Here we identify that TRPV1+ pain-sensing nociceptors co-opt chemosensory epithelial tuft cells to initiate a cascade of tissue responses that drive type 2 inflammation.

Type 2 inflammation at barrier surfaces is an evolutionarily conserved response that promotes immunity to parasites, allergic inflammation and tissue repair. Direct sensing of environmental triggers by epithelial cells initiates type 2 inflammation and signals derived from neurons can modulate immune responses. However, how diverse sensory inputs from epithelial, neuronal and immune cells are coordinated and integrated remains unclear. Here we identify that TRPV1+ pain-sensing nociceptors co-opt chemosensory epithelial tuft cells to initiate a cascade of tissue responses that drive type 2 inflammation.