Coordination of retrotransposons and type I interferon with distinct interferon pathways in dermatomyositis, systemic lupus erythematosus and autoimmune blistering disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 21K20753
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Gunma University
• Principal Investigator: Kuriyama Yuko 群馬大学, 医学部附属病院, 医員 (80910588)
• Project Period (FY): 2021-08-30 – 2022-03-31
• Keywords: インターフェロン / 皮膚筋炎 / 全身性エリテマトーデス

Outline of Final Research Achievements

The correlation between type I interferon (IFN) and retrotransposons contributing to its production in dermatomyositis, systemic lupus erythematosus, and autoimmune blistering, and the correlation with interferon-induced genes downstream of the IFN pathway were clarified for each disease. The expression of retrotransposons and type I IFNs in concert was widely observed from healthy to autoimmune diseases, suggesting that type I IFN expression and retrotransposon expression may be mutually regulated. In patients with dermatomyositis, high type I IFN expression may be induced by increased retrotransposon expression, and abnormal high expression of STAT1 is characteristic of SLE, suggesting that chronic IFN-γ signaling may be involved.

Free Research Field

ウイルス、インターフェロン

Academic Significance and Societal Importance of the Research Achievements

協調したレトロトランスポゾンとI型IFNの発現は健常から自己免疫疾患まで広くみられ、I型IFNの発現とレトロトランスポゾン発現は相互制御である可能性が示唆された。皮膚筋炎患者においてはI型IFN高発現がレトロトランスポゾンの発現亢進によって誘導されることが示唆され、LINE-1発現を抑える５Aza-CやIFN経路の下流を抑えるJAK-STAT経路に関わるpan-JAK阻害薬は有用である可能性があり、今後の治療薬の開発につながる結果である。