Exacerbation of experimental allergic asthma by augmented Th2 responses in WSX-1-deficient mice

Yoshiyuki Miyazaki, Hiromasa Inoue, Mikiko Matsumura, Koichiro Matsumoto, Takako Nakano, Miyuki Tsuda, Shinjiro Hamano, Akihiko Yoshimura, Hiroki Yoshida

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96 Citations (Scopus)

Abstract

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-γ 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.

Original languageEnglish
Pages (from-to)2401-2407
Number of pages7
JournalJournal of Immunology
Volume175
Issue number4
DOIs
Publication statusPublished - 2005 Aug 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Miyazaki, Y., Inoue, H., Matsumura, M., Matsumoto, K., Nakano, T., Tsuda, M., Hamano, S., Yoshimura, A., & Yoshida, H. (2005). Exacerbation of experimental allergic asthma by augmented Th2 responses in WSX-1-deficient mice. Journal of Immunology, 175(4), 2401-2407. https://doi.org/10.4049/jimmunol.175.4.2401