title: Mechanism of NKT cell activation by intranasal coadministration of alpha-galactosylceramide, which can induce cross-protection against influenza viruses.
abstract: In a nasal vaccine against influenza, the activation of natural killer T (NKT) cells by intranasal coadministration of alpha-galactosylceramide (alpha-GalCer) can potently enhance protective immune responses. The results of this study show that the NKT cell-activated nasal vaccine can induce an effective cross-protection against different strains of influenza virus, including H5 type. To analyze the mechanism of NKT cell activation by this nasal vaccine, we prepared fluorescence-labeled alpha-GalCer by which we detect a direct interaction between NKT cells and alpha-GalCer-stored dendritic cells in nasal mucosa-associated tissues. Accordingly, although very few NKT cells exist at mucosa, the nasal vaccination induced a localized increase in NKT cell population, which is partly dependent on CXCL16/CXCR6. Furthermore, we found that NKT cell activation stimulates mucosal IgA production by a mechanism that is dependent on interleukin (IL)-4 production. These results strengthen the basis of nasal vaccination via NKT cell activation, which can induce immune cross-protection.
authors.affiliation: Division of Bioregulation Research, Institute of Medical Science, St Marianna University School of Medicine, Miyamae-ku, Kawasaki City, Kanagawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kamijuku
authors.forename: Y
authors.initials: Y
authors.lastname: Nagata
authors.forename: X
authors.initials: X
authors.lastname: Jiang
authors.forename: T
authors.initials: T
authors.lastname: Ichinohe
authors.forename: T
authors.initials: T
authors.lastname: Tashiro
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
authors.forename: K
authors.initials: K
authors.lastname: Hase
authors.forename: H
authors.initials: H
authors.lastname: Ohno
authors.forename: T
authors.initials: T
authors.lastname: Shimaoka
authors.forename: S
authors.initials: S
authors.lastname: Yonehara
authors.forename: T
authors.initials: T
authors.lastname: Odagiri
authors.forename: M
authors.initials: M
authors.lastname: Tashiro
authors.forename: T
authors.initials: T
authors.lastname: Sata
authors.forename: H
authors.initials: H
authors.lastname: Hasegawa
authors.forename: K-i
authors.initials: KI
authors.lastname: Seino
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000918:Antibody Specificity; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000276:immunology; D003429:Cross Reactions; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005456:Fluorescent Dyes; D005699:Galactosylceramides / Q000008:administration & dosage*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology; D054387:Receptors, CXCR / Q000276:immunology; D000075744:Receptors, CXCR6; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; D005456:Fluorescent Dyes; D005699:Galactosylceramides; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; C493154:alpha-galactosylceramide; D015847:Interleukin-4