The role of IDO in the HBV-related liver diseases.

• Project/Area Number: 24659361
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Gifu University
• Principal Investigator: SEISHIMA Mitsuru 岐阜大学, 医学(系)研究科(研究院), 教授 (10171315)
• Co-Investigator(Kenkyū-buntansha): ITO Hiroyasu 岐阜大学, 大学院医学系研究科, 准教授 (80373075)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: B型肝炎ウイルス / インドールアミン酸素添加酵素 / 細胞傷害性T細胞 / 急性肝炎 / 肝炎ウイルス / 細胞障害性T細胞

Research Abstract

Indoleamine 2, 3-dioxygenase (IDO), an enzyme that is ubiquitously distributed in mammalian tissues and cells, converts tryptophan (Trp) to L-kynurenine (L-Kyn), and it is noted as a relevant molecule in promoting tolerance and suppressing adaptive immunity. In this study, we revealed the role of IDO in the induction of HBV-specific cytotoxic T lymphocyte (CTL) and acute hepatitis induced by HBV-specific CTL. IDO impaired the induction of HBV-specific CTL after immunization with HBsAg and alpha-GalCer. In acute hepatitis model, the inhibition of IDO expression improved the liver injury induced by HBV-specific CTL. These results demonstrated that IDO is critical in the induction of HBV-specific CTL and acute hepatitis. The control of IDO activity leads to a new therapy for diseases caused by HBV infection.

Research Products

• [Journal Article] Induction of HBsAg-specific cytotoxic T lymphocytes can be up-regulated by the inhibition of indoleamine 2, 3-dioxygenase activity (2014)
  • Author(s): Ito H, Ando T, Ando K, Ishikawa T, Saito K, Moriwaki H, Seishima M
  • Journal Title: Immunology Volume: 印刷中 Issue: 4 Pages: 614-623
  • DOI: 10.1111/imm.12274
  • Peer Reviewed
• [Journal Article] Kynurenine production mediated by indoleamine 2, 3-dioxygenase aggravates liver injury in HBV-specific CTL-induced fulminant hepatitis (2014)
  • Author(s): Ohtaki H, Ito H, Ando K, Ishikawa T, Hoshi M, Ando T, Takamatsu M, Hara A, Moriwaki H, Saito K, Seishima M
  • Journal Title: Biochim Biophys Acta Volume: 1842(9) Issue: 9 Pages: 1464-71
  • DOI: 10.1016/j.bbadis.2014.04.015
  • Peer Reviewed
• [Presentation] インドールアミン酸素添加酵素の発現抑制によるHBV特異的細胞障害性T細胞誘導効果 (2013)
  • Author(s): 伊藤弘康、安藤量基、石川哲也、森脇久隆、清島満
  • Organizer: 第40回日本肝臓学会西部会
  • Place of Presentation: 岐阜
• [Presentation] インドールアミン酸素添加酵素の発現制御を用いたHBV特異的細胞障害性T細胞誘導効果の検討 (2013)
  • Author(s): 伊藤弘康、安藤達也、石川哲也、清島満
  • Organizer: 第60回日本臨床検査医学会学術集会
  • Place of Presentation: 神戸
• [Presentation] マウスB型急性肝炎モデルにおけるインドールアミン酸素添加酵素の解析 (2013)
  • Author(s): 伊藤弘康、大瀧博文、安藤達也、安藤量基、石川哲也、森脇久隆、清島満
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] 細胞障害性T細胞により誘発されるマウス劇症肝炎モデルにおけるindoleamine 2, 3-dioxygenaseの解析 (2012)
  • Author(s): 安藤達也、大瀧博文、伊藤弘康、星雅人、石川哲也、斎藤邦明、清島満
  • Organizer: 第59回日本臨床検査医学会学術集会
  • Place of Presentation: 京都
• [Presentation] 細胞障害性T細胞により誘発されるマウス劇症肝炎モデルにおける indoleamine 2, 3-dioxygenaseの解析 (2012)
  • Author(s): 安藤 達也、清島 満ら
  • Organizer: 第59回日本臨床検査医学会学術集会
  • Place of Presentation: 京都
• [Remarks]
  • URL: http://www1.gifu-u.ac.jp/~labmed/