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2007 Fiscal Year Final Research Report Summary

Investigation of novel therapeutic approach through regulatory T cells (Tr) and dendritic cells (DCs) for the patients with autoimmune hepatitis (AIH)

Research Project

Project/Area Number 18590754
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionAichi Medical University

Principal Investigator

OKUMURA Akihiko  Aichi Medical University, School of Medicine, Assistant Professor (70288512)

Co-Investigator(Kenkyū-buntansha) ISHIKAWA Tetsuya  Aichi Medical University, School of Medicine, Assistant Professor (10288508)
KAKUMU Shinichi  Aichi Medical University, School of Medicine, Professor (10115545)
Project Period (FY) 2006 – 2007
Keywordsregulatory T cell (Tr) / autoimmune hepatitis (AIH) / apoptosis / toll-like receptor (TLR) / dendritic cells (DCs) / TNF-R1 / Bad / real time PCR
Research Abstract

(1) Expression of toll-like receptor (TLR) family on Dendritic cells (DCs) in patients with autoimmune hepatitis (AIH). Total RNA was extracted from isolated T-reg and non-T-reg fractions and the amount of mRNA for TLR2, 3, 4, 6, 7, 8, 9were evaluated by real time PCR. TLR3, 6, 7, 9were expressed on circulating myeloid DC (MDC) and plasmacytoid DC (PDC) in controls, while only TLR6was expressed on those in patients with AIH. Thus different expression pattern of TLRs on DCs might have some influence on the pathogenesis of AIH.
(2) Expression of apoptosis-related molecules on DCs, and susceptibility of DCs to apoptosis induced through TNF-R1 in patients with AIH.
Total RNA was extracted from circulating myeloid DC (MDC) and plasmacytoid DC (PDC), the amount of mRNA for TNF-R1, TNF-RS18, Fas, Bcl-2, Bax, Bad, FAST, PKR, Apaf-1, and c-FLIP were evaluated by real time PCR. Further, after incubation of MDC+PDC in the presence of TNFα, susceptibility to apoptosis induced through TNF-R1 was evaluated by counting the number of apoptotic DCs. TNF-RS18, TNF-R1, Bad, and FAST were expressed on freshly isolated MDC and PDC both in AIH and control. However, expression of TNF-R1 and Bad was significantly suppressed in AIH compared with controls. After 72 hour incubation in the presence of TNFα, the amount of apoptotic MDC and PDC in controls increased from 30.0% to 45.8%, whereas that in AIH changed from 33.3% to 34.5%, suggesting the possibility that apoptosis of MDC and PDC induced by signals through TNF-R1 is suppressed in AIH.

  • Research Products

    (8 results)

All 2008 2007

All Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (4 results)

  • [Journal Article] Deficiency of Foxp3 and CTLA-4 gene expression and impaired suppress or function of CD4+CD25+T cells in patients with autoimmune hepatitis2008

    • Author(s)
      Okumura A, et al.
    • Journal Title

      Hepatology Research 38

      Pages: 866-903

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Deficiency of Foxp3 and CTLA-4 gene expression and impaired suppressor function of CD4+CD25+ T cells in patients with autoimmune hepatitis2008

    • Author(s)
      Okumura A, et al.
    • Journal Title

      Hepatology Research 38

      Pages: 866-903

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of Toll-like receptors in chronic hepatitis C virus infection2007

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

      Journal of Gastroenterology and Hepatology 22

      Pages: 1627-1632

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Expression of Toll-like receptors in chronic hepatitis C virus infection2007

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

      J Gastroenterol Hepatol 22

      Pages: 1627-1632

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Dendritic cells in patients with autoimmune hepatitis are resistant to apoptosis induced through TNF receptor2008

    • Author(s)
      Okumura A, et al.
    • Organizer
      Digestive Disease Week 2008
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2008-05-21
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Dendritic cells in patients with autoimmune hepatitis are resistant to apoptosis induced through TNF receptor2008

    • Author(s)
      Okumura A, et al.
    • Organizer
      Digestive Disease Week 2008
    • Place of Presentation
      San Diego
    • Year and Date
      2008-05-21
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 自己免疫性肝炎(AIH)患者の樹状細胞(DC)におけるアポトーシス関連分子の発現〜健常人・C型慢性肝炎患者との比較〜2007

    • Author(s)
      奥村明彦, ら
    • Organizer
      第43回日本肝臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-05-31
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Expression of apoptosis-related molecules on dendritic cells(DCs) in patients with autoimmune hepatitis(AIH).2007

    • Author(s)
      Okumura A, et al.
    • Organizer
      The 43th Annual Meeting of Japan Society of Hepatology
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-05-31
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-06-09  

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