title: IFN-gamma attenuates antigen-induced overall immune response in the airway as a Th1-type immune regulatory cytokine.
abstract: 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.
authors: Department of Allergy and Rheumatology, University of Tokyo, Japan.
authors: Kazuyuki
authors: K
authors: Nakagome
authors: Katsuhide
authors: K
authors: Okunishi
authors: Mitsuru
authors: M
authors: Imamura
authors: Hiroaki
authors: H
authors: Harada
authors: Taku
authors: T
authors: Matsumoto
authors: Ryoichi
authors: R
authors: Tanaka
authors: Jun-ichi
authors: J
authors: Miyazaki
authors: Kazuhiko
authors: K
authors: Yamamoto
authors: Makoto
authors: M
authors: Dohi
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D039521:CD11c Antigen / Q000096:biosynthesis / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000517:prevention & control; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000941:Antigens; D039521:CD11c Antigen; D016207:Cytokines; D007371:Interferon-gamma; D010047:Ovalbumin