Regulation of NKT cell-mediated hepatic injury in mice

• Project/Area Number: 26460990
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kitasato University (2017); Niigata University (2014-2016)
• Principal Investigator: Kawamura Toshihiko 北里大学, 医療衛生学部, 教授 (70301182)
• Co-Investigator(Kenkyū-buntansha): 神田 泰洋 新潟大学, 医歯学系, 助教 (00436768)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: NKT細胞 / 肝炎 / alpha-galactosylceramide / RASAL3 / 骨髄由来抑制細胞 / 肝臓 / 自己免疫性肝炎 / RasGAP

Outline of Final Research Achievements

Treatment of mice with alpha-galactosylcermide, a specific agonist for NKT cells, induces liver injury. To investigate the mechanisms of a-GalCer induced liver injury, we focused on two factors, RASAL3 and MDSC(Myeloid-derive suppressor cells).
1. RASAL3 which is a hematopoietic RasGAP protein, was found to be predominantly expressed in liver NKT cells. Analysis of RASAL3-deficient mice demonstrated that RASAL3 contributes to aggravation of liver injury by regulating NKT cell function.
2. The number of myeloid-derive suppressor cells (MDSC) was increased in the liver of a-GalCer treated mice. These MDCS were found to suppress liver injury by regulating NKT cell activation through the production of inhibitory cytokines.

Research Products

• [Journal Article] RASAL3, a novel hematopoietic RasGAP protein, regulates the number and functions of NKT cells. (2015)
  • Author(s): Saito S, Kawamura T, Higuchi M, Kobayashi T, Yoshita-Takahashi M, Yamazaki M, Abe M, Sakimura K, Kanda Y, Kawamura H, Jiang S, Naito M, Yoshizaki T, Takahashi M, Fujii M.
  • Journal Title: Eur J Immunol. Volume: in press Issue: 5 Pages: 1512-1523
  • DOI: 10.1002/eji.201444977
  • Peer Reviewed