A critical role of IL-33 in experimental allergic rhinitis

Abstract

We reported previously that serum levels of IL-33 are significantly increased in patients with allergic rhinitis (AR). However, very little is known about the role of IL-33 for the development of AR. We thought to develop a novel murine model of ragweed pollen-specific AR and examined the pathologic role for ragweed-induced IL-33 in the development of AR manifestation using IL-33-deficient (il33(-/-)) mice. Ragweed-immunized and ragweed-challenged mice were examined for early- and late-phase nasal responses. IL-33 protein expression in the nasal epithelial cells of the AR murine model and patients with AR were assessed by using confocal microscopy. After nasal challenge with ragweed pollen, ragweed-immunized wild-type mice manifested early-phase (sneezing) and late-phase (eosinophilic and basophilic accumulation) responses. In contrast, il33(-/-) and FcεRI(-/-) mice did not have both early- and late-phase AR responses. IL-33 protein was constitutively expressed in the nucleus of nasal epithelial cells and was promptly released into nasal fluids in response to nasal exposure to ragweed pollen. In human subjects we revealed constitutive expression of IL-33 protein in the nasal epithelial cells of healthy control subjects and downregulated expression of IL-33 protein in inflamed nasal epithelial cells of patients with AR. IL-33-stimulated mast cells and basophils contributed to the early- and late-phase AR manifestation through increasing histamine release and production of chemoattractants for eosinophils/basophils, respectively. Ragweed pollen-driven endogenous IL-33 contributed to the development of AR responses. IL-33 might present an important therapeutic target for the prevention of AR.