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Analysis of the innate immune responses in the liver of patients with chronic hepatitis C following liver transplantation to develop a novel immunotherapy for the recurrent hepatitis C infection

Research Project

Project/Area Number 18590723
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionNiigata University

Principal Investigator

YAMAGIWA Satoshi  Niigata University, Medical and Dental Hospital, Clinical Staff (10419327)

Co-Investigator(Kenkyū-buntansha) MATSUDA Yasunobu  Niigata University, Institute of Medicine and Dentistry, Associate Professor (40334669)
TAKAMURA Masaaki  Niigata University, Medical and Dental Hospital, Clinical Staff (20422602)
SATO Yoshinobu  Niigata University, Institute of Medicine and Dentistry, Lecturer (20313538)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordstransplantation immunology / liver transplantation / natural killer cells / chronic hepatitis C / 移植・再生医療 / 免疫学 / 臨床
Research Abstract

(1) Natural killer (NK) cell subsets in the liver of patients with recurrent hepatitis C following liver transplantation
Human NK cells can be divided into two subsets based on their cell-surface density of CD56 - CD56^(+bright) and CD56^(+dim) - each with distinct phenotypic properties. We investigated the NK cell subsets in the liver of patients with recurrent hepatitis C following living-donor liver transplantation (LDLT). The patients with chronic hepatitis C (CHC) and the donors for LDLT were also investigated as controls. We revealed that the CD56^(+bright) subset was significantly decreased in the liver of patients with recurrent hepatitis C than that in the patients with CHC and the normal donors. The expression of an activation marker CD69 on the CD56^(+dim) subset was significantly increased in the liver of LDLT. Our results suggest that further examination of the status of intrahepatic NK cell subsets might provide a new insight into the mechanism of rapid progression of recurrent hepatitis C infection.
(2) Gene expression profiles in the liver of patients with recurrent hepatitis C following liver transplantation
We investigated the gene expression profiles in the liver of patients with recurrent hepatitis C after LDLT using liver biopsy samples. However, we could not find any significant changes in the gene expression profiles among the recurrent hepatitis C patients and CHC patients yet.
(3) NK and NKT cells in the liver of patients with chronic hepatitis C before and after interferon plus ribavirin therapy
Previous studies have revealed that functional impairment of NK and NKT cells might be associated with the persistence of hepatitis C virus (HCV). However, the involvement of these cells, which predominate in the liver, in therapeutic HCV clearance is still unclear. We found a close relationship between the significant increase of intrahepatic NK/NKT cells and sustained HCV clearance in CHC patients treated with interferon-a plus ribavirin therapy.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (43 results)

All 2008 2007 2006

All Journal Article (30 results) (of which Peer Reviewed: 14 results) Presentation (13 results)

  • [Journal Article] Sustained response to interferon-α plus ribavirin therapy for chronic hepatitis is closely associated with increased dynamism of intrahepatic natural killer and natural killer T cells2008

    • Author(s)
      Yamagiwa S, et. al.
    • Journal Title

      Hepatology Research (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Temporal treatment with interferon-beta prevents hepatocellular carcinoma in hepatitis B virus X gene transgenic mice2008

    • Author(s)
      Yamazaki K, et. al.
    • Journal Title

      Journal of Hepatology 48(2)

      Pages: 255-265

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Sustained response to interferon-α plus ribavirin therapy for chronic hepatitis C is closely associated with increased dynamism of intrahepatic natural killer and natural killer T cells2008

    • Author(s)
      Yamagiwa, S, et. al.
    • Journal Title

      Hepatology Research (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Temporal treatment with interferon-beta prevents hepatocellular carcinoma in hepatitis B virus X gene transgenic mice2008

    • Author(s)
      Yamazaki, K, et. al.
    • Journal Title

      Journal of Hepatology 48(2)

      Pages: 255-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Sustained response to interferon-α plus ribavirin therapy for chronic hepatitis C is closely associated with increased dynamism of intrahepatic natural killer and natural killer T cells2008

    • Author(s)
      Yamagiwa S, et. al.
    • Journal Title

      Hepatology Research (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recurrence of primary biliary cirrhosis and primary sclerosing cholangitis afterliver transplantation in Japan2007

    • Author(s)
      Yamagiwa S, Ichida T.
    • Journal Title

      Hepatology Research 37(Supple3)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Altered expression of TLR homolog RP105 on monocytes hypersensitive to LPS in patients with primary biliary cirrhosis2007

    • Author(s)
      Honda Y, Yamagiwa S, et. al.
    • Journal Title

      Journal of Hepatology 47(3)

      Pages: 404-411

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 potentates the antigen-independent growth of human hepatoma HepG2 cells2007

    • Author(s)
      Hokari M, et. al.
    • Journal Title

      Life Science 81(4)

      Pages: 336-345

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Blockade of interferon-gamma-inducible protein-10 attenuates chronic experimentalcolitis by blocking cellular trafficking and protecting intestinal epithelial cells2007

    • Author(s)
      Suzuki K, et. al.
    • Journal Title

      Pathology International 57(7)

      Pages: 413-420

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] An inhibitor of c-Jun NK2-terminal kinase, SP600125, protects mice from D-galactosamine/lipopolysaccharide-induced hepatic failure by modulating BH3-only proteins2007

    • Author(s)
      Takamura M, et. al.
    • Journal Title

      Life Science 80(14)

      Pages: 1335-1344

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 【診断ピットフォール 症例から学ぶ】消化器 かゆみ2007

    • Author(s)
      山際 訓, 他
    • Journal Title

      内科 99(6)

      Pages: 1156-1165

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Recurrence of primary biliary cirrhosis and primary sclerosing cholangitis after liver transplantation in Japan2007

    • Author(s)
      Yamagiwa, S, Ichida, T
    • Journal Title

      Hepatology Research 37(3)

      Pages: 449-54

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Altered expression of TLR homolog RP105 on monocytes hypersensitive to LPS in patients with primary biliary cirrhosis2007

    • Author(s)
      Honda, Y, Yamagiwa, S, et. al.
    • Journal Title

      Journal of Hepatology 47(3)

      Pages: 404-11

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Blockade of interferon-gamma-inducible protein-10 attenuates chronic experimental colitis by blocking cellular trafficking and protecting intestinal epithelial cells2007

    • Author(s)
      Suzuki, K, et. al.
    • Journal Title

      Pathology International 57(7)

      Pages: 413-20

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Recurrence of primary biliary cirrhosis and primary sclerosing cholangitis after liver transplantation in Japan2007

    • Author(s)
      Yamagiwa S, Ichida T.
    • Journal Title

      Hepatology Research 37(Suppl 3)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 potentates the anchorage-independent growth of human hepatoma HepG2 cells2007

    • Author(s)
      Hokari M, et. al.
    • Journal Title

      Life Science 81(4)

      Pages: 336-345

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An inhibitor of c-Jun NH2-terminal kinase, SP600125, protects mice from D-galactosa mine/lipopolysaccharide-induced hepatic failure by modulating BH3-only proteins2007

    • Author(s)
      Takamura M, et. al.
    • Journal Title

      Life Science 80(14)

      Pages: 1335-1344

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of interferon gamma-iuducible protein-10 attenuates chronic experimental colitis by blocking cellular trafficking and protecting intestinal epithelial cells2007

    • Author(s)
      Suzuki K, et. al.
    • Journal Title

      Pathology Tnternational 57(7)

      Pages: 413-420

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An inhibitor of c-Jun NH2-terminal kinase, SP600125, protects mice from D-galactosamine/lipopolysaccharide-induced hepatic failure by modulating BH3-only proteins.2007

    • Author(s)
      Takamura M, et al.
    • Journal Title

      Life Science 80(14)

      Pages: 1335-1344

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Increase of CD4^+CD25^+ regulatory T-cells in the liver of patients with hepatocellular carcinoma2006

    • Author(s)
      Yang XH, Yamagiwa S, et. al.
    • Journal Title

      Journal of Hepatology 45(2)

      Pages: 254-262

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] MEK/ERK signaling is a critical mediator for integrin-induced cell scattering in highly metastatic hepatocellular carcinoma2006

    • Author(s)
      Honma N, et. al.
    • Journal Title

      Laboratory Investigation 86(7)

      Pages: 687-696

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A primary follicular lymphoma of the duodenum treacd successfully with radiation therapy2006

    • Author(s)
      Takamura M, et. al.
    • Journal Title

      Internal Medicine 45(5)

      Pages: 309-311

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] PBC病態における自然免疫の関与2006

    • Author(s)
      山際 訓, 他
    • Journal Title

      肝胆膵 52(4)

      Pages: 563-570

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 自然免疫抑制による移植肝に対する免疫寛容誘導2006

    • Author(s)
      富山智香子, 他
    • Journal Title

      肝胆膵 52(4)

      Pages: 607-615

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 比較的若年の女性に起こった原因不明の肝静脈閉塞症の1例2006

    • Author(s)
      塙 孝泰, 他
    • Journal Title

      臨床消化器内科 21(8)

      Pages: 1197-1202

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Increase of CD4^+CD25^+ regulatory T-cells in the liver of patients with hepatocellular carcinoma.2006

    • Author(s)
      Yang XH, et al.
    • Journal Title

      Journal of Hepatology 45(2)

      Pages: 254-262

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Role of IP-lO/CXCL1O in the progression of pancreatitis-like injury in mice after murine retroviral infection.2006

    • Author(s)
      Kawauchi Y, et al.
    • Journal Title

      American Journal of Physiology - Gastrointestinal and Liver physiology 291(2)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] MEK/ERK signaling is a critical mediator for integrin-induced cell scattering in highly metastatic hepatocellular carcinoma cells.2006

    • Author(s)
      Honma N, et al.
    • Journal Title

      Laboratory Investigation 86(7)

      Pages: 687-696

    • Related Report
      2006 Annual Research Report
  • [Journal Article] PBC病態における自然免疫の関与・2006

    • Author(s)
      山際 訓, 他.
    • Journal Title

      肝胆膵 52(4)

      Pages: 563-570

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 自然免疫制御による移植肝に対する免疫寛容誘導.2006

    • Author(s)
      富山智香子, 他.
    • Journal Title

      肝胆膵 52(4)

      Pages: 607-615

    • Related Report
      2006 Annual Research Report
  • [Presentation] 肝移植後C型慢性肝炎再発における肝内NK細胞の関与2008

    • Author(s)
      山際 訓, 他
    • Organizer
      第44回日本肝臓学会総会
    • Place of Presentation
      愛媛県県民文化会館(松山市)
    • Year and Date
      2008-06-06
    • Related Report
      2007 Annual Research Report
  • [Presentation] 原発性胆汁性肝硬変におけるToll-like receptor homolog RP105の発現とLPS高反応性2007

    • Author(s)
      山際 訓, 他
    • Organizer
      第43回日本肝臓学会総会
    • Place of Presentation
      ホテルグランパシフィックメリディアン(東京都)
    • Year and Date
      2007-05-31
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Recurrence of PBC and PSC after living donor liver transplantation in Japan2007

    • Author(s)
      Yamagiwa S, et. al.
    • Organizer
      第17回アジア太平洋肝臓学会総会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2007-03-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Recurrence of PBC and PSC after living donor liver transplantation in Japan2007

    • Author(s)
      Yamagiwa, S, Ichida, T
    • Organizer
      The 17th APASL
    • Place of Presentation
      at Kyoto
    • Year and Date
      2007-03-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] CD81 signaling is not associated with increased expression of NKG2A on NK cells in CHC patients2007

    • Author(s)
      Yamagiwa S, et. al.
    • Organizer
      第17回アジア太平洋肝臓学会総会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2007-03-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] CD81 signaling is not associated with increased expression of NKG2A on NK cells in CHC patients2007

    • Author(s)
      Yamagiwa, S, el al
    • Organizer
      The 17th APASL
    • Place of Presentation
      at Kyoto
    • Year and Date
      2007-03-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 新潟大学関連施設におけるC型慢性肝炎に対するPEG-IFNα-2a療法の現状と血清CXCL10による治療効果予測2006

    • Author(s)
      山際 訓, 他
    • Organizer
      第10回日本肝臓学会大会(DDW-Japan 2006)
    • Place of Presentation
      道立総合体育センター(札幌市)
    • Year and Date
      2006-10-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Recurrence of PBC and PSC after liver transplantation in Japan2006

    • Author(s)
      Yamagiwa S, et. al.
    • Organizer
      第5回日本肝臓学会シングルトピックカンファレンス
    • Place of Presentation
      ベストウェスタンプレミアホテル長崎(長崎市)
    • Year and Date
      2006-09-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Recurrence of PBC and PSC after liver transplantation in Japan2006

    • Author(s)
      Yamagiwa, S, Ichida, T
    • Organizer
      The 5th JSH single topic conference
    • Place of Presentation
      at Nagasaki
    • Year and Date
      2006-09-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Altered expression of RP105 and Toll-like receptor-4 may increase the. monocyteresponse to lipopolysaccharide in patients with primary biliary cirrhosis2006

    • Author(s)
      Yamagiwa S, et. al.
    • Organizer
      第5回日本肝臓学会シングルトピックカンファレンス
    • Place of Presentation
      ベストウェスタンプレミアホテル長崎(長崎市)
    • Year and Date
      2006-09-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Altered expression of RP105 and Toll-like receptor-4 may increase the monocyte response to lipopolysaccharide in patients with primary biliary cirrhosis2006

    • Author(s)
      Yamagiwa, S,, et. al.
    • Organizer
      The 5th JSH single topic conference
    • Place of Presentation
      at Nagasaki
    • Year and Date
      2006-09-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] C型慢性肝炎症例のNK細胞におけるNKG2A高発現とその機序2006

    • Author(s)
      山際 訓, 他
    • Organizer
      第42回日本肝臓学会総会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2006-05-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] CXCL10によるC型慢性肝炎に対するPEG化インターフェロン治療効果予測2006

    • Author(s)
      山際 訓, 他
    • Organizer
      第103回日本内科学会総会学術講演会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2006-04-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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