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Immune response to dermatomyositis-specific autoantigen, transcriptional intermediary factor 1γ can result in experimental myositis
  1. Naoko Okiyama1,
  2. Yuki Ichimura1,
  3. Miwako Shobo1,
  4. Ryota Tanaka1,
  5. Noriko Kubota1,
  6. Akimasa Saito1,
  7. Yosuke Ishitsuka1,2,
  8. Rei Watanabe1,2,
  9. Yasuhiro Fujisawa1,
  10. Yoshiyuki Nakamura1,
  11. Akihiro Murakami3,
  12. Hisako Kayama4,
  13. Kiyoshi Takeda5,
  14. Manabu Fujimoto1,6
  1. 1Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
  2. 2Department of Integrative Medicine for Allergic and Immunological Disease, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
  3. 3Medical and Biological Laboratories Co Ltd, Nagoya, Aichi, Japan
  4. 4Institute for Advanced Co-Creation Studies, Osaka University, Suita, Osaka, Japan
  5. 5Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
  6. 6Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
  1. Correspondence to Dr Naoko Okiyama, Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan; naoko.okiyama{at}


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, β2-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.

  • dermatomyositis
  • autoantibodies
  • T-lymphocyte subsets

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • Handling editor Josef S Smolen

  • Contributors Study concept and design: NO and MF. Acquisition and analysis and interpretation of data: all authors. Drafting of the manuscript: NO and MF. Critical revision of the manuscript for important intellectual content: NO and YI. Obtained funding: NO and MF.

  • Funding Supported by KAKENHI from the Japan Society for the Promotion of Science (JSPS, 18K08263 for Naoko Okiyama).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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