Alpha-Galactosylceramide-Induced Airway Eosinophilia Is Mediated through the Activation of Nkt Cells

Invariant NKT iNKT cells bridge innate and adaptive immune responses, resulting in the expansion of Ag-specific B and T cell responses. alpha- Galactosylceramide alpha-GalCer, the most studied glycolipid that activates iNKT cells, has been proposed to be an effective adjuvant against infections and tumors. We found that the activation of iNKT cells by intranasal injection of alpha-GalCer induced airway eosinophilia in naive mice. Eosinophils, which mediate tissue damage and dysfunction by secreting mediators, play important roles in the pathogenesis of allergic diseases. In this study, we investigated the mechanism of how eosinophils are recruited to the lung by alpha-GalCer. Our results demonstrated that alpha-GalCer-induced eosinophil inflammation was mediated through iNKT cells. These cells secreted IL-5 to recruit eosinophils directly to the lung and/or secreted IL-4 and IL-13 to recruit eosinophils indirectly by inducing lung epithelial cells, endothelial cells, and fibroblast to secrete the eosinophil chemoattractant eotaxin. In addition, in the OVA- alum murine model of allergic asthma, alpha-GalCer administration in OVA- immunized mice also increased airway eosinophilia after challenge. Given our findings, intranasal administration of alpha-GalCer induced airway eosinophilic inflammation in both naive and allergic mice. Hence, it remains to be determined whether the activation of iNKT cells would be applicable in therapeutics for human diseases