017 Immunization of dermatomyositis-specific autoantigen transcriptional intermediary factor (TIF1)-γ induces experimental myositis in mice

      A number of myositis-specific autoantigens have been identified in dermatomyositis patients. While murine models of experimental myositis have been established using immunizations of muscle-specific proteins like myosin and C protein, they are not targeted in actual diseases. Here we established a new murine model of experimental myositis inducible with immunizations of TIF1-γ, one of self-antigens for myositis-specific autoantibodies. We purified recombinant whole human TIF1-γ protein using baculovirus expression systems, and immunized wild-type C57BL/6J (B6) mice with subcutaneous injections of emulsions containing the protein and complete Freund's adjuvant four times. Myositis was observed in bilateral muscles of the immunized mice 14 days after the last immunizations. The lymph node T cells from the mice proliferated when stimulated with TIF1-γ, and IgG reacting TIF1-γ were detected in the sera of the mice. Adoptive transfer of the T cells from the mice stimulated with TIF1-γ could cause myositis in naïve B6 mice. Moreover, transfer of the purified CD8+ T cells, but not the purified CD4+ T cells, caused define myositis in naïve B6 mice (the incidences: 90 % and 0 %, respectively). β2 microglobulin-deficient mice, which lack major histocompatibility complex I, and perforin-deficient mice, in which CD8+ T cells lack cytotoxicity, developed significantly weaker myositis than wild-type mice (myositis scores: 0.13 ± 0.23, 0.30 ± 0.48, and 0.91 ± 0.70, respectively). Transfer of IgG collected from TIF1-γ-immunized mice could not cause myositis in naïve B6 mice, moreover, μMT (B cell-deficient) mice developed myositis after TIF1-γ immunizations with no inferiority compared to wild-type mice. Collectively, TIF1-γ is an autoantigen with especial immunogenicity to induce experimental myositis, in which the muscle injury is directly mediated by CD8+ T cells, but not CD4+ T cells or antibodies. TIF1-γ-induced experimental myositis would be an useful tool to investigate pathology of anti-TIF1-γ antibody-associated dermatomyositis.