The analysis on the correlation between Fli1 downregulation and innate immune system dysregulation in the pathogenesis of systemic sclerosis

• Project/Area Number: 15H06165
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: The University of Tokyo
• Principal Investigator: TAKAHASHI Takehiro 東京大学, 医学部附属病院, 助教 (30755690)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 全身性強皮症 / 自然免疫 / TLR4 / 免疫異常 / 自己免疫 / Fli1

Outline of Final Research Achievements

Systemic sclerosis (SSc), or scleroderma, is a chronic connective tissue disease characterized by three cardinal features: autoimmunity/inflammation, vasculopathy, and fibrosis in the skin and various internal organs. Although SSc pathogenesis remains elusive, genetic studies have demonstrated the central role of immune abnormalities in SSc development. In particular, recent researches have disclosed the cardinal role of innate immune system dysregulation in the pathogenesis of autoimmune diseases including SSc.
Numerous studies from our laboratory and others have demonstrated the critical role of Friend leukemia virus integration 1 (Fli1), a member of the Ets transcription factor family, in SSc pathogenesis. This time, we studied on the correlation between Fli1 and dysregulation in the innate immune system in SSc, and indeed could demonstrate their profound relationship in its pathogenesis.

Research Products

• [Journal Article] Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma. (2017)
  • Author(s): Takehiro Takahashi, Yoshihide Asano, Koji Sugawara, Kouki Nakamura, Takashi Yamashita, Ryosuke Saigusa, Yohei Ichimura, Tetsuo Toyama, Takashi Taniguchi, Kaname Akamata, Shinji Noda, Ayumi Yoshizaki, Daisuke Tsuruta, Maria Trojanowska, and Shinichi Sato
  • Journal Title: Journal of Experimental Medicine Volume: 214 Issue: 4 Pages: 1129-1151
  • DOI: 10.1084/jem.20160247
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A possible contribution of lipocalin-2 to the development of dermal fibrosis, pulmonary vascular involvement and renal dysfunction in systemic sclerosis. (2015)
  • Author(s): Takehiro Takahashi, Yoshihide Asano, Shinji Noda, Naohiko Aozasa, Kaname Akamata, Takashi Taniguchi, Yohei Ichimura, Tetsuo Toyama, Hayakazu Sumida, Yoshihiro Kuwano, Yayoi Tada, Makoto Sugata, Takafumi Kadono, Shinichi Sato
  • Journal Title: British Journal of Dermatology Volume: 173 Issue: 3 Pages: 681-9
  • DOI: 10.1111/bjd.13779
  • Peer Reviewed