Exacerbation of experimental allergic asthma by augmented Th2 responses in WSX-1-deficient mice.
WSX-1 (IL-27R) is a class I cytokine receptor with homology to gp130 and IL-12 receptors and is typically expressed on CD4+ T lymphocytes. Although previous reports have clarified that IL-27/WSX-1 signaling plays critical roles in both Th1 differentiation and attenuation of cell activation and proinflammatory cytokine production during some bacterial or protozoan infections, little is known about the importance of WSX-1 in cytokine-mediated diseases of allergic origin. To this aim, we took advantage of WSX-1-deficient (WSX-1(-/-)) mice and induced experimental asthma, in which Th2 cytokines are central modulators of the pathology. OVA-challenged WSX-1(-/-) mice showed marked enhancement of airway responsiveness with goblet cell hyperplasia, pulmonary eosinophil infiltration, and increased serum IgE levels compared with wild-type mice. Production of Th2 cytokines, which are largely responsible for the pathogenesis of asthma, was augmented in the lung or in the culture supernatants of peribronchial lymph node CD4+ T cells from WSX-1(-/-) mice compared with those from wild-type mice. Surprisingly, IFN-gamma production was also enhanced in WSX-1(-/-) mice, albeit at a low concentration. The cytokine overproduction, thus, seems independent from the Th1-promoting property of WSX-1. These results demonstrated that IL-27/WSX-1 also plays an important role in the down-regulation of airway hyper-reactivity and lung inflammation during the development of allergic asthma through its suppressive effect on cytokine production.
Miyazaki
Yoshiyuki
Y
PRESTO, Japan Science and Technology Agency, Saitama, Japan.
Inoue
Hiromasa
H
Matsumura
Mikiko
M
Matsumoto
Koichiro
K
Nakano
Takako
T
Tsuda
Miyuki
M
Hamano
Shinjiro
S
Yoshimura
Akihiko
A
Yoshida
Hiroki
H
D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001980:Bronchi / Q000276:immunology / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004804:Eosinophils / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D018123:Receptors, Interleukin; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology; D020825:T-Box Domain Proteins; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics* / Q000276:immunology*; D000098815:T-bet Transcription Factor
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; C484747:Il27ra protein, mouse; D018793:Interleukin-13; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D050826:Suppressor of Cytokine Signaling Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D007073:Immunoglobulin E; D007371:Interferon-gamma