Control of liver fibrosis after transplantation by immunomodulation

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390322
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyoto University
• Principal Investigator: KOJIRO Taura 京都大学, 医学(系)研究科(研究院), 助教 (80378629)
• Co-Investigator(Kenkyū-buntansha): UEMOTO Shinji 京都大学, 医学研究科, 教授 (40252449) ; HATANO Etsuro 京都大学, 医学研究科, 講師 (80359801)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 肝線維化 / 肝移植 / 脾臓 / 免疫

Research Abstract

To investigate the effects of splenectomy on liver fibrosis, BALB/c mice underwent splenectomy or sham operation and subjected to carbon tetrachloride (CCl4) or thioacetamide (TAA) treatments. Splenectomy significantly suppressed liver fibrosis in the CCl4 and TAA models. The inhibitory effect of splenectomy on liver fibrosis was not observed in SCID mice.
To investigate the mechanisms underlying these effects, we investigated the change of liver Th1/Th2 balance. As a result, splenectomy shifted Th1/Th2 balance toward Th1-dominance. In addition, the number of CD4+ lymphocytes in the spleen was decreased. In contrast, that in the liver was increased. GFP+ splenic lymphocytes were transplanted into the spleen of wild type mice. GFP+CD4+ lymphocytes appeared in the liver after induction of fibrosis and the vast majority of them were Th2 lymphocytes by flow cytometry.
We conclude that splenectomy suppresses progression of liver fibrosis at least partly through restoring the Th1/Th2 balance.

Research Products

• [Journal Article] The impact of posthepatectomy liver failure on the recurrence of hepatocellular carcinoma (2014)
  • Author(s): Iguchi K, Hatano E, Yamanaka K, Tanaka S, Taura K, Uemoto S
  • Journal Title: World J Surg Volume: 38(1) Pages: 150-158
  • DOI: 10.1007/s00268-013-2247-7
  • Peer Reviewed
• [Journal Article] Direct volume manipulation for visualizing intraoperative liver resection process (2014)
  • Author(s): Nakao M, Oda Y, Taura K, Minato K
  • Journal Title: Comput Methods Programs Biomed Volume: 113(3) Pages: 725-735
  • DOI: 10.1016/j.cmpb.2013.12.004
  • Peer Reviewed
• [Journal Article] Effect of olprinone on liver microstructure in rat partial liver transplantation (2013)
  • Author(s): Yamanaka K, Hatano E, Iguchi K, Yamamoto G, Sato M, Toriguchi K, Tanabe K, Takemoto K, Nakamura K, Koyama N, Narita M, Nagata H, Taura K, Uemoto S
  • Journal Title: J Surg Res Volume: 183(1) Pages: 391-396
  • DOI: 10.1016/j.jss.2012.11.033
  • Peer Reviewed
• [Journal Article] Effects of oral intake of hydrogen water on liver fibrogenesis in mice (2013)
  • Author(s): Koyama Y, Taura K, Hatano E, Tanabe K, Yamamoto G, Nakamura K, Yamanaka K, Kitamura K, Narita M, Nagata H, Yanagida A, Iida T, Iwaisako K, Fujinawa H, Uemoto S
  • Journal Title: Hepatol Res
  • DOI: 10.1111/hepr.12165
  • Peer Reviewed
• [Journal Article] Soluble thrombomodulin attenuates sinusoidal obstruction syndrome in rat through suppression of high mobility group box 1 (2013)
  • Author(s): Nakamura K, Hatano E, Miyagawa-Hayashino A, Okuno M, Koyama Y, Narita M, Seo S, Taura K, Uemoto S
  • Journal Title: Liver Int
  • DOI: 10.1111/liv.12420
  • Peer Reviewed
• [Presentation] 脾臓摘出術は肝臓におけるTh1/Th2 サイトカインバランスの変化を介して肝線維化を抑制する (2014)
  • Author(s): 田邉和孝, 田浦康二朗, 波多野悦朗, 小山幸法, 山本玄, 西尾太宏, 奥田雄紀浩, 中村公治郎, 鳥口寛, 竹本研史, 上本伸二
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 20140403-05
• [Presentation] 肝静脈根部大型肝癌に対する肝切除術式 (2014)
  • Author(s): 田浦康二朗, 波多野悦朗, 安近健太郎, 瀬尾智, 福光剣, 上本伸二
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 20140403-05
• [Presentation] Migration of splenic lymphocytes promotes fibrotic response in the liver through modification of T helper cytokine balance in mice (2014)
  • Author(s): K. Tanabe, K. Taura, Y. Koyama, G. Yamamoto, T. Nishio, E. Hatano, S. Uemoto
  • Organizer: Academic Surgical Congress
  • Place of Presentation: Manchester Grand Hyatt (San Diego, CA)
  • Year and Date: 20140204-06
• [Presentation] Liver Stiffness Measurement Predicts Posthepatectomy Liver Failure (2014)
  • Author(s): K. Taura, Y. Koyama, K. Tanabe, G. Yamamoto, T. Nishio, E. Hatano, S. Uemoto
  • Organizer: Academic Surgical Congress
  • Place of Presentation: Manchester Grand Hyatt (San Diego, CA)
  • Year and Date: 20140204-06