Production of both IL-27 and IFN-gamma after the treatment with a ligand for invariant NK T cells is responsible for the suppression of Th2 response and allergic inflammation in a mouse experimental asthma model

• Published in: The Journal of immunology (1950) 2009-07, Vol.183 (1), p.254-260
• Main Authors: Fujita, Hiroyuki, Teng, Annabelle, Nozawa, Risa, Takamoto-Matsui, Yukiko, Katagiri-Matsumura, Haruka, Ikezawa, Zenro, Ishii, Yasuyuki
• Format: Article
• Language: English
• Subjects: Animals; Asthma - immunology; Asthma - pathology; Asthma - prevention & control; Cells, Cultured; Disease Models, Animal; Female; Galactosylceramides - administration & dosage; Galactosylceramides - metabolism; Galactosylceramides - physiology; Hypersensitivity - immunology; Hypersensitivity - pathology; Hypersensitivity - prevention & control; Immunosuppression; Inflammation Mediators - administration & dosage; Inflammation Mediators - metabolism; Inflammation Mediators - physiology; Injections, Intraperitoneal; Interferon-gamma - biosynthesis; Interferon-gamma - physiology; Interleukins - biosynthesis; Interleukins - physiology; Ligands; Mice; Mice, Inbred BALB C; Mice, Knockout; Natural Killer T-Cells - immunology; Natural Killer T-Cells - metabolism; Th2 Cells - drug effects; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0800520

Using an allergen-induced airway inflammation model, we show that an injection of alpha-galactosylceramide (alpha-GalCer), a ligand for invariant NK T (iNKT) cells, induced IL-27 and that this process is essential for the attenuation of the Th2 response. After the systemic administration of alpha-GalCer into the mice primed with OVA in alum, Th2 cytokine production of OVA-primed CD4(+) T cells in their lymph nodes, IgG1 and IgE Ab formation, and infiltration of eosinophils in bronchoalveolar lavage after the OVA challenge were suppressed. Systemic administration of rIFN-gamma into OVA-primed mice could not reproduce these effects of alpha-GalCer. IL-27p28 was detected both in the culture supernatant of alpha-GalCer-stimulated spleen cells and in the serum of the alpha-GalCer-treated mice, but not in the iNKT cell-deficient mice. Splenic iNKT cells produced IL-27p28 in the culture supernatant upon stimulation with PMA plus ionomycin, although the transcript of IL-27p28 in the iNKT cells was constitutively expressed regardless of the stimulation. By contrast, the transcript of IL-27EBI3 was induced in the iNKT cells upon stimulation with PMA plus ionomycin in vitro and with alpha-GalCer treatment in vivo, suggesting that IL-27 (p28/EBI3) could be produced by iNKT cells in an activation-dependent manner. Although repeated injections of rIL-27 did not substitute for the effects of a single injection of alpha-GalCer, administration of rIL-27 along with rIFN-gamma reproduced in vivo effects of the alpha-GalCer injection. These data indicate that production of both IL-27 and IFN-gamma by the alpha-GalCer treatment is responsible for suppression of the Th2 response and allergic inflammation.