The Novel Role of T cell in Liver Ischemia and Reperfusion Injury

• Project/Area Number: 23791527
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyoto University
• Principal Investigator: UCHIDA Yoichiro 京都大学, 医学(系)研究科(研究院), 非常勤講師 (30597745)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 虚血再灌流障害 / 肝臓 / Galectin-9 / TIM / T細胞 / TLR-4 / 肝移植 / マクロファージ / 自然免疫 / 国際情報交換 / アメリカ / ガレクチン / 国際情報交流

Research Abstract

This study was performed to investigate the novel role of T cell in liver ischemia and reperfusion injury (IRI), focued on T cell Immunoglobulin Mucin (TIM) molecules. In our established 70% partial warm liver IR model for C57BL/6 mice, treated with PBS or stable Galectin-9 (Gal-9 is a TIM-3 ligand), the serum ALT level and histological findings in Gal-9 treated group were significantly ameliorated compared to PBS treated groups. The induction of cytokines (IL-6, INF-r, CXCL-1, CXCL-2) and apoptotic positive cells by TUNEL staining in the liver was decreased in Gal-9 treated groups. Gal-9 might be protective for liver IRI through the inhibition of T cell activation.

Research Products

• [Journal Article] Progressive graft fibrosis and donor-specific HLA antibodies in pediatric late liver allografts (2012)
  • Author(s): Miyagawa-Hayashino A, Yoshizawa A, Uchida Y, Egawa H, Yurugi K, Masuda S, Minamiguchi S, Maekawa T, Uemoto S, Haga H.
  • Journal Title: Liver Transpl Volume: 18 Pages: 1333-1342
  • Peer Reviewed
• [Journal Article] Interleukin-22 : Implications for Liver Ischemia-Reperfusion Injury (2012)
  • Author(s): Chestovich PJ, Uchida Y, Chang W, Ajalat M, Lassman C, Sabat R, Busuttil RW, Kupiec-Weglinski JW.
  • Journal Title: Transplantation Volume: 93 Pages: 485-492
  • Peer Reviewed
• [Journal Article] Type I Interferon Pathway Mediates Renal Ischemia/Reperfusion Injury (2011)
  • Author(s): Freitas MC, Uchida Y, Lassman C, Danovitch GM, Busuttil RW, Kupiec-Weglinski JW.
  • Journal Title: Transplantation Volume: 92 Pages: 131-138
  • Peer Reviewed
• [Journal Article] Native macrophages genetically modified to express heme oxygenase 1 protect rat liver transplants from ischemia/reperfusion injury (2011)
  • Author(s): Shen XD, Ke B, Uchida Y, Ji H, Gao F, Zhai Y, Busuttil RW, Kupiec-Weglinski JW.
  • Journal Title: Liver Transpl Volume: 17 Pages: 201-210
  • Peer Reviewed
• [Journal Article] Association of anti-HLA and anti-Angiotensin II Type 1 Receptor Antibodies with Liver Allograft Fibrosis after Immunosuppression Withdrawal
  • Author(s): Ohe H, Uchida Y, Yoshizawa A, Hirao H, Taniguchi M, Maruya E, Yurugi K, Hishida R, Maekawa T, Uemoto S, Terasaki PI.
  • Journal Title: Transplantation Volume: (in press)
  • Peer Reviewed
• [Journal Article] Whey-hydrolyzed peptide-enriched immunomodulating diet prevents progression of liver cirrhosis in rats
  • Author(s): Jobara K, Kaido T, Hori T, Iwaisako K, Endo K, Uchida Y, Uemoto S.
  • Journal Title: Nutrition Volume: (in press)
  • Peer Reviewed
• [Presentation] 肝虚血再灌流障害におけるIL-22の保護効果 (2013)
  • Author(s): 内田洋一朗、加茂直子、平尾浩史、田中宏和、寺嶋宏明、Ronald W. Busuttil、Jerzy W. Kupiec-Weglinski、上本伸二
  • Organizer: 第113回日本外科学会定期学術集会
• [Presentation] 肝虚血再灌流障害におけるTIM-3(T-Cell Immunoglobulin Mucin-3)とGalectin-9およびTLR-4とのCross-Talk (2012)
  • Author(s): 内田洋一朗、加茂直子、Ronald W. Busuttil、Jerzy W. Kupiec-Weglinski、上本伸二
  • Organizer: 第112回日本外科学会定期学術集会
• [Presentation] 肝虚血再灌流障害におけるT Cell Ig Mucin-3 (TIM-3)の役割 (2011)
  • Author(s): 内田洋一朗、加茂直子、Ronald W. Busuttil、Jerzy W. Kupiec-、上本伸二
  • Organizer: 第111回日本外科学会定期学術集会