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.
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.
Fujita
Hiroyuki
H
RIKEN Research Center for Allergy and Immunology, Suehiro, Tsurumi, Yokohama, Kanagawa, Japan.
Teng
Annabelle
A
Nozawa
Risa
R
Takamoto-Matsui
Yukiko
Y
Katagiri-Matsumura
Haruka
H
Ikezawa
Zenro
Z
Ishii
Yasuyuki
Y
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage* / Q000378:metabolism / Q000502:physiology; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007165:Immunosuppression Therapy; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000378:metabolism / Q000502:physiology; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000502:physiology; D007378:Interleukins / Q000096:biosynthesis* / Q000502:physiology; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D005699:Galactosylceramides; C486767:Il27 protein, mouse; D018836:Inflammation Mediators; D007378:Interleukins; D008024:Ligands; C493154:alpha-galactosylceramide; D007371:Interferon-gamma