オクニシ　カツヒデ   Okunishi Katsuhide   奥西　勝秀    所属   東邦大学  医学部 医学科    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	IFN-gamma attenuates antigen-induced overall immune response in the airway as a Th1-type immune regulatory cytokine.
掲載誌名	正式名：Journal of immunology (Baltimore, Md. : 1950) ISSNコード：0022-1767
掲載区分	国外
出版社	AMER ASSOC IMMUNOLOGISTS
巻・号・頁	183(1),pp.209-20
著者・共著者	Kazuyuki Nakagome,Katsuhide Okunishi,Mitsuru Imamura,Hiroaki Harada,Taku Matsumoto,Ryoichi Tanaka,Jun-ichi Miyazaki,Kazuhiko Yamamoto,Makoto Dohi
発行年月	2009/07/01
概要	Allergic inflammation in the airway is generally considered a Th2-type immune response. However, recent studies demonstrated that Th1- and Th17-type immune responses also play important roles in this process. IFN-gamma is a Th1-type cytokine that generally counteracts the Th2 response. Although previous studies suggest that exogenous IFN-gamma suppresses allergic airway inflammation, the mechanism of suppression has not been fully clarified. In this study, we elucidated whether IFN-gamma suppresses Ag-induced immune responses including the production of Th1- and Th17-type cytokines in the lung, and examined its mechanism of action. BALB/c mice were sensitized and challenged with OVA-Ag to induce airway inflammation. An IFN-gamma-producing plasmid vector was delivered before systemic Ag sensitization. IFN-gamma suppressed indicators of Th2-type immune responses such as airway eosinophilia, IL-5 and IL-13 production in the lung, and bronchial mucus production. Moreover, IFN-gamma also suppressed the production of IL-17 and IFN-gamma itself. The suppression was not mediated by inducing regulatory T cells or by inducing apoptosis in immunocytes. Instead, IFN-gamma suppressed the Ag-presenting capacity and cytokine production of splenic dendritic cells and thus subsequently suppressed OVA-induced activation of CD4(+) T cells. Furthermore, IFN-gamma also attenuated allergic airway inflammation when delivered during the OVA challenge. Various functions of lung CD11c(+) APCs and their migration to regional lymph nodes were also suppressed. These results suggest that the Th1 cytokine IFN-gamma has broad immune regulatory potential through suppressing APC functions. They also suggest that delivery of IFN-gamma could be an effective strategy for regulating Ag-induced immune responses in the lung.
DOI	10.4049/jimmunol.0802712
PMID	19542432