Asthma is a heterogenous inflammatory disease characterized by massive infiltration of neutrophils or eosinophils into the lungs after exposure to allergens or other noxious agents. In Neuron, Talbot et al. reveal a role for lung nociceptor neurons in amplifying type 2 (eosinophilic) allergic responses. Airway allergen challenge induces the release of IL-5, which is recognized by Nav1.8+ nociceptor neurons that express IL-5 receptors. These lung nociceptors respond to IL-5 by releasing the vasoactive peptide VIP. Type 2 innate lymphoid cells and TH2 cells recognize this mediator via its receptor VPAC2, which elicits the release of IL-5, IL-13 and other type 2 mediators. This response leads to further recruitment of TH2 cells, eosinophils and macrophages into the inflammed lungs and thereby drives a feed-forward amplication loop that exacebates type 2 eosinophilic asthma. Notably, inhibition or ablation of lung nociceptors does not alter TH1 cell–mediated lung inflammation. Therapeutic strategies that can interfere with this amplification loop might therefore offer relief to some asthmatic people.

Neuron 87, 341–354 (2015)