Type 2 inflammation at barrier surfaces is an evolutionarily conserved response that promotes immunity to helminth parasites, allergic inflammation and tissue repair1–4. Direct sensing of environmental triggers by epithelial cells initiates type 2 inflammation, and signals derived from neurons can modulate immune responses5–8. 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. Chemogenetic silencing or chemical ablation of TRPV1+ nociceptors results in a significant reduction in intestinal tuft cells and defective anti-helminth type 2 immunity. By contrast, chemogenetic activation of TRPV1+ nociceptors leads to remodelling of CGRP+ nerve fibres, significantly increased CGRP expression, enhanced tuft cell accumulation and protective anti-helminth type 2 immunity. Using spatial transcriptomic and single-cell RNA sequencing analyses, we reveal that nociceptor activation promotes rapid epithelial progenitor cell proliferation and differentiation. Mechanistically, intestinal epithelial cell-intrinsic and tuft cell-intrinsic expression of CGRP receptor subunits are required for tuft cell responses and type 2 immunity to helminth infection. Together, these results identify sensory convergence of a neuronal–epithelial tuft cell circuit as a critical upstream determinant of type 2 immunity and tissue adaptation.
