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Elucidation of molecular mechanism of specific immune memory and development of therapeutic strategy for autoimmune diseases

Research Project

Project/Area Number 17K10005
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionDokkyo Medical University

Principal Investigator

Arima Masafumi  獨協医科大学, 医学部, 准教授 (00202763)

Co-Investigator(Kenkyū-buntansha) 福島 康次  獨協医科大学, 医学部, 教授 (00254996)
幡野 雅彦  千葉大学, 大学院医学研究院, 教授 (20208523)
谷口 俊文  千葉大学, 医学部附属病院, 講師 (20724826)
倉沢 和宏  獨協医科大学, 医学部, 教授 (30282479)
杉山 公美弥  獨協医科大学, 医学部, 教授 (30364582)
大和田 高義  獨協医科大学, 医学部, 講師 (30456016)
平田 博国  獨協医科大学, 医学部, 准教授 (60326890)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords自己免疫疾患 / SLE / ADAR1
Outline of Final Research Achievements

To clarify the role of the double-stranded RNA editing enzyme ADAR1 (adenosine deaminase acting on RNA-1) in the pathology of autoimmune diseases, we analyzed the systemic lupus erythematosus (SLE) model in mice that specifically lack ADAR1 in activated T cells, B cells, and macrophages, respectively. Mice lacking ADAR1 specifically in activated T cells or B cells had reduced SLE pathologies (nephritis, anti-dsDNA antibody titers, germinal center formation and Tfh cell differentiation in lymphoid tissues). The function of ADAR1 in macrophages was not clear. These results revealed that ADAR1 functions in T cells and B cells and is involved in adaptive immunity. It is considered that the abnormal function of ADAR1 in the adaptive immune system, especially its increased function, may cause an increase in autoantibody production, leading to the development of autoimmune diseases such as SLE.

Academic Significance and Societal Importance of the Research Achievements

免疫応答におけるリンパ球の機能制御にはダイナミックな遺伝子発現とRNA修飾が関わっているが、その詳細なメカニズムは明らかでない。自己免疫疾患における疾患特異的獲得免疫機能の詳細も不明のままである。我々は、獲得免疫における機能が明らかでないADAR1に注目し、本研究により獲得免疫機能にADAR1が関与することを見出した。また、T細胞およびB細胞におけるADAR1の機能調節機能の解明が、今後の自己免疫疾患の病態研究に繋がる可能性を示した。本研究成果は、免疫システムの解明研究の発展に貢献する点に意義がある。またSLEなど難治性自己免疫疾患に対する新規治療薬の開発へとつながる点に社会的意義がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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