Immune response to dermatomyositis-specific autoantigen, transcriptional intermediary factor 1γ can result in experimental myositis.

Objectives: To investigate whether autoimmunity to transcriptional intermediary factor 1 (TIF1)γ, a ubiquitous nuclear autoantigen for myositis-specific autoantibodies detected in patients with dermatomyositis (DM) is pathogenetic for inflammatory myopathy.
Methods: Wild-type, β ₂ -microglobulin-null, perforin-null, Igμ-null and interferon α/β receptor (IFNAR)-null mice were immunised with recombinant human TIF1γ whole protein. A thymidine incorporation assay was performed using lymph node T cells from TIF1γ-immunised mice. Plasma was analysed using immunoprecipitation followed by western blot analysis and enzyme-linked immunosorbent assays. Femoral muscles were histologically and immunohistochemically evaluated. CD8 ⁺ or CD4 ⁺ T cells isolated from lymph node T cells or IgG purified from plasma were adoptively transferred to naïve mice. TIF1γ-immunised mice were treated with anti-CD8 depleting antibody and a Janus kinase inhibitor, tofacitinib.
Results: Immunisation with TIF1γ-induced experimental myositis presenting with necrosis/atrophy of muscle fibres accompanied by CD8 ⁺ T cell infiltration successfully in wild-type mice, in which TIF1γ-specific T cells and antihuman and murine TIF1γ IgG antibodies were detected. The incidence and severity of myositis were significantly lower in β₂-microglobulin-null, perforin-null, CD8-depleted or IFNAR-null mice, while Igμ-null mice developed myositis normally. Adoptive transfer of CD8 ⁺ T cells induced myositis in recipients, while transfer of CD4 ⁺ T cells or IgG did not. Treatment with tofacitinib inhibited TIF1γ-induced myositis.
Conclusions: Here we show that TIF1γ is immunogenic enough to cause experimental myositis, in which CD8 ⁺ T cells and type I interferons, but not CD4 ⁺ T cells, B cells or antibodies, are required. This murine model would be a tool for understanding the pathologies of DM.
Competing Interests: Competing interests: None declared.
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