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Development of therapy for chronic hepatitis C using interferon-producing dendritic cells

Research Project

Project/Area Number 14570474
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

S.M.F. Akbar  Ehime University School of Medicine, Third Department of Internal Medicine, Instructor, 医学部, 助手 (90294793)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsPlasmacytoid DC / Myeloid DCs / Chronic hepatitis C / Interferon-alpha / Polarization of naive CD4+ naive T cells / plasmacytoid樹状細胞 / myeloid樹状細胞 / インターフェロン産生細胞 / C型肝炎ウイルス / 樹状細胞
Research Abstract

In this study, we evaluated the frequencies and functions of myeloid dendritic cell (MDC) and interferon (IFN)-producing plasmacytoid DC (PDC). The frequencies of MDC and PDC in the peripheral blood of 63 patients with chronic hepatitis C (CHC) and 34 normal control subjects were estimated by 4-color flow cytometry. Furthermore, we also checked the production of IFN-alpha by MDC in 10 patients with CHC and 10 normal control subjects. The capacity of MDC to polarize naive CD4^+ T cells to IFN-gamma-producing effector T cells were also evaluated in 10 patients with CHC and 10 control subjects.
The levels of IFN-alpha produced by PDC from patients with CHC were significantly lower compared to that of, normal control subjects (p<0.05). This was confirmed by evaluating the production of intracellular IFN-alpha in PDC, production of IFN-alpha in culture and from the expression levels of IFN-alpha. The frequencies of MDCs were significantly lower in patients with CHC compared to that in normal control subjects. MDC from patients with CHC also had impaired capacity to induce polarization of naive CD4^+ T cells to IFN-gamma-producing T cells. Taken, together, this study shows that impaired functions of PDC and MDC might be responsible for the low anti-HCV immune responses in CHC patients. Improvement of the function of PDCs in CHC patients might contribute to new immune therapy for CHC patients.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Tsubouchi E, Akbar SMF, Horiike N, Onji M.: "Infection and dysfunction of circulating blood dendritic cells and their subsets in chronic hepatitis C virus infection."J Gastroenterol. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kumagi T, Akbar SMF, Horiike N, Onji M.: "Increased survival and decreased tumor size due to intratumoral injection of ethanol followed by administration of immature dendritic cells."Int J Oncol. 23. 949-955 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe M, Akbar SMF, Horiike N, Onji M.: "Inability of liver dendritic cells from mouse with experimental hepatitis to process and present specific antigens."Hepatol Res. 26. 61-67 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arima S, Akbar SMF, Michitaka K, Horiike N, Nuriya H, Kohara M, Onji M.: "Impaired function of antigen-presenting dendritic cells in patients with chronic hepatitis B : Localization of HBV DNA and HBV RNA in blood DC by in situ hybridization."Int J Mol Med. 11. 169-174 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe M, Akbar SMF, Horiike N, Onji M.: "Defective antigen-presenting cell capacity of murine dendritic cells due to starvation."Nutrition. 19. 265-269 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Murakami H, Akbar SMF, Matsui H, Horiike N, Onji M.: "Macrophage migration inhibitory factor activates antigen-presenting dendritic cells and induces inflammatory cytokines in ulcerative colitis."Clin Exp Immunol. 128. 504-510 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akbar SMF, Horiike N, Onji M.: "Recent Research Developments in Immunology"Research Signpost. 695-702 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsubouchi E, Akbar SMF, Horiike N, Onji M.: "Infection and dysfunction of circulating blood dendritic cells and their subsets in chronic hepatitis C virus infection."Journal of Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kumagi T, Akbar SMF, Horiike N, Onji M.: "Increased survival and decreased tumor size due to intratumoral injection of ethanol followed by administration of immature dendritic cells."International Journal of Oncology. 23. 949-955 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe M, Akbar SMF, Horiike N, Onji M.: "Inability of liver dendritic cells from mouse with experimental hepatitis to process and present specific antigens."Hepatology Research. 26. 61-67 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arima S, Akbar SMF, Michitaka K, Horiike N, Nuriya H, Kohara M, Onji M.: "Impaired function of antigen-presenting dendritic cells in patients with chronic hepatitis B : Localization of HBV DNA and HBV RNA in blood DC by in situ hybridization."International Journal of Molecular Medicine. 11. 169-174 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe M, Akbar SMF, Horiike N, Onji M.: "Defective antigen-presenting cell capacity of murine dendritic cells due to starvation."Nutrition. 19. 265-269 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Murakami H, Akbar SMF, Matsui H, Horiike N, Onji M.: "Macrophage migration inhibitory factor activates antigen-presenting dendritic cells and induces inflammatory cytokines in ulcerative colitis."Clinical and Experimental Immunology. 128. 504-510 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Akbar SMF, Horiike N, Onji M.: Recent Research Developments in Immunology. Research Signpost. 695-702 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsubouchi B, Akbar SMF, Horiike N, Onji M.: "Infection and dysfunction of circulating blood dendritic cells and their subsets in chronic hepatitis C virus infection."J Gastroenterol. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Kumagi T, Akbar SMF, Horiike N, Onji M.: "Increased survival and decreased tumor size due to intratumoral injection of ethanol followed by administration of immature dendritic cells."Int J Oncol. 23. 949-955 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Abe M, Akbar SMF, Horiike N, Onji M.: "Inability of liver dendritic cells from mouse with experimental hepatitis to process and present specific antigens."Hepatol Res. 26. 61-67 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arima S, Akbar SMF, Michitaka K, Horiike N, Nuriya H, Kohara M, Onji M.: "Impaired function of antigen-presenting dendritic cells in patients with chronic hepatitis B : Localization of HBV DNA and HBV RNA in blood DC by in situ hybridization."Int J Mol Med. 11. 169-174 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Abe M, Akbar SMF, Horiike N, Onji M.: "Defective antigen-presenting cell capacity of murine dendritic cells due to starvation."Nutrition. 19. 265-269 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arima, S., Akbar SMF, Michitaka, K., Horiike N., Nuriya, H., Kohara, M., Onji.M.: "Impaired function of antigen-presenting dendritic cells in patients with chronic hepatitis B: Localization of HBVDNA and HBVRNA in blood DC by in situ hybridization"International Journal of Molecular Medicine. 11. 169-174 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamauchi, K., Akbar SMF, Horiike, N., Mivhitaka, K., Onji, M.: "Increased serum levels of macrophage inflammatory protein-3α in hepatocellular carcioma: Relationship with clinical factors and prognostic importance during therapy."International Journal of Molecular Medicine. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikeda, Y., Akbar SMF, Matsui, H., Murakami, H., Onji, M.: "Depletion and decreased function of antigen-presenting dendritic cells due to lymphocytapheresis in ulcerative colitis."Diseases of the Rectum and Colon. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Abe, M., Akbar SMF, Horiike, N., Onji, M.: "Defective antigen-presenting cell capacity of murine dendritic cells due to startvation."Nutrition. 19. 265-269 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murakami, H., Akbar SMF, Matsui, H., Horiike, N., Onji, M.: "Macrophage migration inhibitory factor activates antigen-presenting deridritic cells and induces inflammatory cytokine in ulcerative colitis"Clinical and Experimental Immunology. 128. 504-510 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Abe, M., Kajino, K., Akbar SMF, Yamamura, KI., Onji, M., Hino, 0.: "Loss of immunogenecity of liver dendritic cells in mouse with chronic hepatitis."International Journal of Molecular Medicine. 9. 71-76 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akbar SMF, Horiike, N., Onji, M.: ""RECENT ADVANCES IN IMMUNOLOGY""RESEARCH SIGNPOST, KERALA, INDIA (in press).

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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