C型慢性肝炎に対する樹状細胞が産生する内因性インターフェロンを用いた治療法の開発

• 研究課題/領域番号: 14570474
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 消化器内科学
• 研究機関: 愛媛大学
• 研究代表者: AKBAR S.M.F. (S・M・F Akbar) 愛媛大学, 医学部, 助手 (90294793)
• 研究期間 (年度): 2002 – 2003
• 研究課題ステータス: 完了 (2003年度)
• 配分額: 3,400千円 (直接経費: 3,400千円); 2003年度: 1,200千円 (直接経費: 1,200千円); 2002年度: 2,200千円 (直接経費: 2,200千円)
• キーワード: plasmacytoid DC / myeloid DC / C型慢性肝炎 / インターフェロンα / naive CD4^+T細胞活性化能 / 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

研究概要

ヒト末梢血中には極めて大量の内因性1型インターフェロン(IFN)を産生するplasmacytoid樹状細胞(DC)と抗原提示能の高いmyeloid DCが存在する.C型肝炎ウイルス(HCV)の持続感染にそれらのDC機能低下が関与していることを明らかにすることを目的に,plasmacytoid DCの1型IFN産生能とmyeloid樹状細胞のnaive CD4^+T細胞活性化能を解析した.
63人のC型慢性肝炎(CH-C)患者末梢血から単核球を分離し,4カラーフローサイトメトリー法でplasmacytoid DCとmyeloid DCを同定した.末梢血単核球に占めるそれぞれの割合と末梢血中の絶対数を健常者34名と比較した.Plasmacytoid DCによる1型IFN産生能は,1型単純ヘルペスウイルス(HSV-1)刺激による細胞内IFN-α産生細胞数で評価した.Myeloid DCによるnaive CD4^+T細胞活性化能は,DCによるIFN-γ産生活性化T細胞誘導能で評価した.
Plasmacytoid DCの末梢血単核球に占める割合と絶対数はCH-C患者と健常者で差はなかった.CH-C患者のplasmacytoid DCによるIFN-α産生能は健常者に比べて有意に低下していた.CH-C患者末梢血におけるmyeloid DC数は健常者に比べて有意に減少していた.さらに,CH-C患者におけるmyeloid DCのnaive CD4^+T細胞活性化能も,健常者に比べて有意に低下していた.
CH-C患者の末梢血plasmacytoid DCによるIFN-α産生能とmyeloid DCによるnaive CD4^+T細胞活性化能がHCVの持続感染に関与している可能性が示唆された.

研究成果

• [文献書誌] 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.
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Akbar SMF, Horiike N, Onji M.: "Recent Research Developments in Immunology"Research Signpost. 695-702 (2002)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Akbar SMF, Horiike N, Onji M.: Recent Research Developments in Immunology. Research Signpost. 695-702 (2002)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] 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).
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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).
• [文献書誌] 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).
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] 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)
• [文献書誌] Akbar SMF, Horiike, N., Onji, M.: ""RECENT ADVANCES IN IMMUNOLOGY""RESEARCH SIGNPOST, KERALA, INDIA (in press).