IL-6 induced by double-stranded RNA augments allergic inflammation via suppression of Foxp3+T-cell/IL-10 axis

Koichiro Matsumoto, Yukari Asai, Satoru Fukuyama, Keiko Kan-o, Yuko Matsunaga, Naotaka Noda, Hiroko Kitajima, Kentaro Tanaka, Yoichi Nakanishi, Hiromasa Inoue

研究成果: Contribution to journalArticle

8 被引用数 (Scopus)

抄録

Activation of innate immunity against viruses in the respiratory tracts affects the development of asthma. Most respiratory viruses generate double-stranded (ds)RNA during their replication. We recently showed that a low-dose administration of polyinosinic polycytidylic acid (poly IC), a mimetic of viral dsRNA, during allergen sensitization augments airway eosinophilia and hyperresponsiveness in mice via enhanced production of IL-13 from T cells. However, a phenotype of asthma under severer load of dsRNA remains unknown. D-galactosamine (D-GalN) is known as a strong sensitizer of poly IC. Mice weretreated with poly IC plus D-GalN during allergen sensitization. A sublethal dose of poly IC/D-GalN augmented airway eosinophilia and CD4+ T-cell accumulation in the lungs but not airway hyperresponsiveness. The augmented inflammation was associated with decreased IL-10 in the bronchoalveolar lavage fluid and decreased Foxp3+ regulatory T cells in the lungs. Serum IL-6 was prominently higher in the mice treated with poly IC/D-GalN than in that with poly IC alone or D-GalN alone. Poly IC/D-GalN did not affect IL-17-producing T cells in the lungs. Poly IC/D-GalN failed to augment airway eosinophilia after anti-IL-10 receptor monoclonal antibody treatment during allergen challenge. Finally, anti-IL-6 receptor monoclonal antibody treatment before poly IC/D-GalN completely prevented the decrease of IL-10 and Foxp3 + regulatory T cells and the augmentation of airway inflammation. These results indicate that enhanced production of IL-6 by poly IC/D-GalN induces the augmentation of allergic inflammation via suppression of Foxp3 + regulatory T-cell/IL-10 axis. IL-6 may be a target for preventing asthma augmentation related to severevirus infection.

本文言語英語
ページ(範囲)740-747
ページ数8
ジャーナルAmerican journal of respiratory cell and molecular biology
46
6
DOI
出版ステータス出版済み - 6 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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