title: Interferon-γ, but Not Interleukin-4, Suppresses Experimental Polymyositis.
abstract: C protein-induced myositis (CIM) is a mouse model of polymyositis in which activated antigen-specific CD8+ T cells injure the muscles. Animal models of autoimmunity that have been examined in the past for the effects of the type 1 cytokine interferon-γ (IFNγ) and the type 2 cytokine interleukin-4 (IL-4) are all mediated by pathogenic CD4+ T cells. In those models, the disruption of IFNγ leads to up-regulation of IL-17A, exacerbating the disease with neutrophil infiltration into sites of inflammation. This study was undertaken to investigate the roles of IFNγ and IL-4, as well as IL-17A in the absence of IFNγ, in CD8+ T cell-mediated CIM.
  
  
  
  IFNγ(-/-) mice, anti-IL-17A antibody-treated IFNγ(-/-) mice, IFNγ(-/-) IL-17A(-/-) mice, IL-4(-/-) mice, and wild-type C57BL/6 mice were immunized with skeletal muscle C protein fragments to induce CIM. Muscle tissue specimens were examined histologically.
  
  
  
  IFNγ(-/-) mice developed myositis at a higher incidence and with greater severity than wild-type mice. Unlike wild-type mice, IFNγ(-/-) mice had infiltration of neutrophils into the endomysial sites of the affected muscles. IFNγ(-/-) mice treated with anti-IL-17A antibodies and IFNγ(-/-) IL-17A(-/-) mice developed myositis with an incidence and severity comparable to those in IFNγ(-/-) mice and showed neutrophil infiltration similar to that in IFNγ(-/-) mice. IL-4(-/-) mice developed CIM comparable to that in wild-type mice.
  
  
  
  Our findings indicate that IFNγ, but not IL-4, plays a suppressive role in the development of CIM. Unlike in CD4+ T cell-mediated autoimmune disease models, IFNγ prevents factors other than IL-17A from exacerbating myositis and neutrophil infiltration in CD8+ T cell-mediated CIM.
authors.affiliation: Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshihashi-Nakazato
authors.affiliation: Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Tokyo, Japan.
authors.forename: Kimito
authors.initials: K
authors.lastname: Kawahata
authors.affiliation: Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kimura
authors.affiliation: Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.affiliation: Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Tokyo, Japan, and RIKEN Yokohama Institute, Yokohama, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kohsaka
mesh_terms: D000818:Animals; D007371:Interferon-gamma / Q000502:physiology*; D020381:Interleukin-17 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017285:Polymyositis / Q000209:etiology*
chemical_list: D020381:Interleukin-17; D015847:Interleukin-4; D007371:Interferon-gamma