Background: It is well known that Th2 cells and group 2 innate lymphoid cells (ILC2s) contribute to allergic diseases. However, their exact role and relationship in nasal allergic disorders is unclear. We sought to investigate the cooperation of Th2 cells and ILC2s in a mouse model of nasal allergic disorder.
Methods: To differentially activate Th2 cells and/or ILC2s in nasal mucosa, mice were intranasally administered ovalbumin (OVA) antigen, papain, an ILC2-activatior, or both for 2 weeks. Epithelial thickness and number of eosinophils in the nasal mucosa were evaluated at 24 hours after the final challenge.
Results: Intranasal administration of OVA and papain preferentially activated Th2 cells and ILC2s, respectively, in the nose. Both OVA and papain increased the nasal epithelial thickness and number of eosinophils, and their coadministration significantly enhanced the symptoms. Although Rag2-deficient mice showed severely decreased the nasal epithelial thickness and number of eosinophils induced by OVA or OVA-plus-papain, the mice still showed slight papain-induced nasal symptoms. In ILC2-deficient mice, OVA-plus-papain-induced nasal symptoms were suppressed to the same level as OVA-alone. IL-33-deficient mice showed decreased OVA-plus-papain-induced, but not OVA-alone-induced nasal epithelial thickening and eosinophilia. IL-5 induced eosinophilia only, but IL-13 contributed to both nasal epithelial thickening and eosinophilia induced by OVA-plus-papain; notably, this thickening does not require eosinophilia.
Conclusions: Papain-induced ILC2s activated by IL-33 additively exacerbate Th2-cell-induced nasal type 2 inflammation. Furthermore, IL-13, but not IL-5 and eosinophils, contributes to exacerbation of nasal type 2 inflammation.