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α-galactosylceramide-induced airway eosinophilia is mediated through the activation of NKT cells
Journal
Journal of Immunology
Journal Volume
186
Journal Issue
8
Pages
4687-4692
Date Issued
2011
Author(s)
Abstract
Invariant NKT (iNKT) cells bridge innate and adaptive immune responses, resulting in the expansion of Ag-specific B and T cell responses. α-Galactosylceramide (α-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 α-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 α-GalCer. Our results demonstrated that α-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, α-GalCer administration in OVA-immunized mice also increased airway eosinophilia after challenge. Given our findings, intranasal administration of α-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. Copyright ? 2011 by The American Association of Immunologists, Inc.
SDGs
Other Subjects
alpha galactosylceramide; eotaxin; interleukin 13; interleukin 4; interleukin 5; airway eosinophilia; allergic asthma; animal cell; animal experiment; animal model; animal tissue; article; cell function; cell infiltration; cell interaction; controlled study; cytokine release; disease association; endothelium cell; eosinophil count; female; fibroblast; inflammation; inflammatory infiltrate; Loeffler pneumonia; lung alveolus cell; lung infiltrate; mouse; natural killer T cell; nonhuman; priority journal; T lymphocyte activation; Administration, Intranasal; Alum Compounds; Animals; Antigens, CD1d; Asthma; Bronchoalveolar Lavage Fluid; Cells, Cultured; Chemokines, CC; Enzyme-Linked Immunosorbent Assay; Eosinophilia; Eosinophils; Female; Galactosylceramides; Interleukin-13; Interleukin-4; Interleukin-5; Lung; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Knockout; Natural Killer T-Cells; Ovalbumin; Reverse Transcriptase Polymerase Chain Reaction
Type
journal article