Development of therapeutic strategy based on the functional regulation of TFH cells for systemic lupus erythematodes

• Project/Area Number: 18K08413
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Dokkyo Medical University
• Principal Investigator: Kurasawa Kazuhiro 獨協医科大学, 医学部, 教授 (30282479)
• Co-Investigator(Kenkyū-buntansha): 有馬 雅史 獨協医科大学, 医学部, 教授 (00202763) ; 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) ; 大和田 高義 獨協医科大学, 医学部, 講師 (30456016)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 自己免疫疾患 / SLE / c-Myb / 全身性エリテマトーデス / cMyb / ｃ－Myb

Outline of Final Research Achievements

To clarify the role of the transcriptional factor c-Myb in the pathology of autoimmune diseases, we analyzed the systemic lupus erythematosus (SLE) model in mice that　specifically lack c-Myb in activated T cells. Mice lacking c-Myb specifically in activated T cells had modified SLE like pathologies (nephritis, anti-dsDNA antibody titers, germinal center formation and Tfh cell differentiation in lymphoid tissues). These results revealed that c-Myb functions in especially GC-Tfh cells and Treg cells and is involved in adaptive immunity. It is considered that the abnormal functional balance between GC-Tfh cells and Treg cells due to the pathological abnormal function of c-Myb may lead to the development of autoimmune diseases such as SLE.

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患の疾患特異的獲得免疫機構におけるリンパ球の機能制御の詳細なメカニズムは未だ明らかでない。我々は、獲得免疫におけるヘルパーT細胞、とりわけTfh細胞およびTreg細胞において機能が明らかでないc-Mybについて注目し、本研究により獲得免疫機能にc-Mybが関与することを見出した。また、T細胞におけるc-Myb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。

Research Products

• [Journal Article] Auto-antibody evaluation in idiopathic interstitial pneumonia and worse survival of patients with Ro52/TRIM21auto-antibody (2020)
  • Author(s): Morita H, Shimizu Y, Nakamura Y, Okutomi H, Watanabe T, Yokoyama T, Soda S, Ikeda N, Shiobara T, Miyoshi M, Chibana K, Takemasa A, Kurasawa K.
  • Journal Title: J Clin Biochem Nutr. Volume: 67 Issue: 2 Pages: 199-205
  • DOI: 10.3164/jcbn.20-5
  • NAID: 130007894910
  • Peer Reviewed / Open Access
• [Presentation] TCZ might be a risk factor for worsening of ILD, particularly of chronic ILD. (2020)
  • Author(s): Tanaka A, Owada T, Hasegawa A, Hiyama T, Takamura Y, Miyao T, Yamazaki R, Arai S, Maezawa R, Arima M, Kurasawa K.
  • Organizer: EULAR (European League Against Rheumatism)
  • Int'l Joint Research
• [Presentation] The Association Between Continuous Decreases in Serum RF Titers and Radiographic Remission of Joint Damage in RA Patients Treated with Biological or Targeted Synthetic DMARDs (2020)
  • Author(s): Owada T, Tanaka A, Hirata H, Arima M, Fukushima Y, Kurasawa K.
  • Organizer: ACR (American College of Rheumatology’s Annual Meeting)
  • Int'l Joint Research