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

ABSTRACT: Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with refractory pain in patients, yet the function of the nervous system in EoE pathogenesis remains ill-defined. 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. Finally, EoE patient samples show increased esophageal neuronal density when compared with controls. Our findings thus describe a type 2 neuroimmune circuit that potentially contributes to EoE pathogenesis, including pain.

ORGANISM(S): Mus musculus

PROVIDER: GSE304046 | GEO | 2026/08/25

REPOSITORIES: GEO

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