Essential role of B7-H1 in double-stranded RNA-induced augmentation of an asthma phenotype in mice

Koichiro Matsumoto, Keiko Kan-o, Miyuki Eguchi-Tsuda, Satoru Fukuyama, Yukari Asai, Takafumi Matsumoto, Atsushi Moriwaki, Yuko Matsunaga, Hiroko Tsutsui, Taro Kawai, Osamu Takeuchi, Shizuo Akira, Hideo Yagita, Miyuki Azuma, Yoichi Nakanishi, Hiromasa Inoue

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12 Citations (Scopus)


Clinical and epidemiological studies have shown the contribution of viral infection to the development of allergic asthma. Many RNA viruses, pathogenic for the respiratory tract, generate doublestranded (ds)RNA during their replication. Typical innate immune responses triggered by dsRNA involve the endosomal and cytoplasmic pathways. The former is mediated by Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF), and the latter by IFN-β promoter stimulator 1 (IPS-1).Weexplored the effect of polyinocinic polycytidilic acid, a synthetic dsRNA, on the development of an asthma phenotype in mice. Administration of dsRNA during ovalbumin sensitization augmented airway eosinophilia and airway hyperresponsiveness after an antigen challenge, which was associated with enhanced induction of IL-13-producing CD8+ T cells. The augmentation was induced in IPS-1-deficient mice but not in TRIFdeficient mice. The interactions between dendritic cells (DCs) and T cells are regulated by B7-family costimulatory molecules, including B7-H1 (also known as PD-L1), a putative ligand for programmed death-1 (PD-1). Treatment ofbonemarrow- derivedDCswithdsRNA enhanced B7-H1 expression in a TRIF-dependent manner. Additionally, dsRNAincreasedB7-H1expressiononDCsin the draininglymph nodes of ovalbumin-sensitized mice. The augmentation of the asthma phenotype was prevented by the treatment of mice with anti-B7-H1mAbbut not with anti-PD-1mAb.Theaugmentationwas not induced in B7-H1-deficient mice. These results suggest that dsRNA-triggered activation of the innate immune system in sensitization leads to augmentation of the asthma phenotype via IL-13 mainly from CD8+ T cells. B7-H1 plays a crucial role in the process without requiring interaction with PD-1.

Original languageEnglish
Pages (from-to)31-39
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Issue number1
Publication statusPublished - Jul 1 2011

All Science Journal Classification (ASJC) codes

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


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