A Neuroimmune Circuit that Regulates Allergic Inflammation in the Esophagus in Mice

Here we elucidate a mouse neuroimmune circuit that is linked to type 2-associated allergic inflammation and clinical responses in the esophagus, including pain. In a mouse allergy model, allergen exposure evokes pain-like behavior, increases esophageal Nav1.8+ sensory innervation density, and alters nociceptor sensitization.

Thoracic dorsal root ganglia (DRG) show allergen-induced expression of type 2 cytokine receptors Il4ra and Il13ra1, while IL-4 and IL-13 sensitize DRG neurons to noxious agents. Mechanistically, conditional deletion of Il4ra in mouse NaV1.8+ neurons attenuate the above allergen-induced phenotypes as well as the levels of insulin-like growth factor 1 (IGF1); in parallel, IGF-1 receptor inhibition also dampens these disease features.