Essential role of B7-H1 in double-stranded RNA-induced augmentation of an asthma phenotype in mice.
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 double-stranded (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). We explored 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 TRIF-deficient 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 of bone marrow-derived DCs with dsRNA enhanced B7-H1 expression in a TRIF-dependent manner. Additionally, dsRNA increased B7-H1 expression on DCs in the draining lymph nodes of ovalbumin-sensitized mice. The augmentation of the asthma phenotype was prevented by the treatment of mice with anti-B7-H1 mAb but not with anti-PD-1 mAb. The augmentation was 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.
Matsumoto
Koichiro
K
Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Kan-O
Keiko
K
Eguchi-Tsuda
Miyuki
M
Fukuyama
Satoru
S
Asai
Yukari
Y
Matsumoto
Takafumi
T
Moriwaki
Atsushi
A
Matsunaga
Yuko
Y
Tsutsui
Hiroko
H
Kawai
Taro
T
Takeuchi
Osamu
O
Akira
Shizuo
S
Yagita
Hideo
H
Azuma
Miyuki
M
Nakanishi
Yoichi
Y
Inoue
Hiromasa
H
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D060890:B7-H1 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology*; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000009:adverse effects / Q000494:pharmacology; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D010641:Phenotype; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012330:RNA, Double-Stranded / Q000009:adverse effects* / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D018793:Interleukin-13; D008562:Membrane Glycoproteins; D010047:Ovalbumin; D010455:Peptides; D012330:RNA, Double-Stranded; C498919:Cd274 protein, mouse; C512612:MAVS protein, mouse; C476286:Ticam1 protein, mouse