Development of immunotherapy using features of innate immunity and liver dendritic cells

• Project/Area Number: 21790669
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Ehime University
• Principal Investigator: ABE Masanori Ehime University, 大学院・医学系研究科, 寄附講座准教授 (40432786)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 樹状細胞 / 肝臓 / 自然免疫

Research Abstract

In this study, we conducted basic research for the development of immunotherapy using liver dendritic cells (DC) and innate immunity. We found that, due to the hyporesponsiveness to endotxin, liver DC stimulated by innate immune signal had less immunogenicity compared to DC from other organs both in vitro and in vivo. These data indicate that it is necessary to consider the balance between maintenance and break endotoxin tolerance for the development of immunotherapy in liver diseases.

Research Products

• [Journal Article] Mechanisms of restoration of immune responses of chronic hepatitis B patients during lamivudine therapy : increased antigen processing and presentation by dendritic cells. (2011)
  • Author(s): Akbar SMF, Horiike N, Chen S, Michitaka K, Abe M, Hiasa Y, Matsuura B, Onji M.
  • Journal Title: J Viral Hepat 18 Pages: 200-205
• [Journal Article] Safety and immunogenicity of hepatitis B surface antigen-pulsed dendritic cells in patients with chronic hepatitis B. (2011)
  • Author(s): Akbar SM, Abe M, et al.
  • Journal Title: J Viral Hepat Volume: 18(in press)
  • Peer Reviewed
• [Journal Article] Impaired dendritic cells functions disrupt antigen-specific adaptive immune responses in mice with nonalcoholic fatty liver disease. (2010)
  • Author(s): Miyake T, Akbar SMF, Yoshida O, Chen S, Hiasa Y, Matsuura B, Abe M, Onji M.
  • Journal Title: J Gastroenterol 45 Pages: 859-867
  • NAID: 10026610917
• [Journal Article] Regulatory natural killer cells in murine liver and their immunosuppressice capacity. (2010)
  • Author(s): Yoshida O, Akbar SMF, Chen S, Miyake T, Abe M, Murakami H, Hiasa Y, Onji M.
  • Journal Title: Liver Int 30 Pages: 906-912
• [Journal Article] Safety and immunogenicity of hepatitis B surface antigen-pulsed dendritic cells in patients with chronic hepatitis B. (2010)
  • Author(s): Akbar SMF, Furukawa S, Horiike N, Abe M, Hiasa Y, Onji M.
  • Journal Title: J Viral Hepat Epub ahead of print
• [Journal Article] Immune modulator and antiviral potential of dendritic cells pulsed with both hepatitis B surface antigen and core antigen for treating chronic HBV infection. (2010)
  • Author(s): Akbar SM, Abe M, et al.
  • Journal Title: Antivir Ther Volume: 15 Pages: 887-895
  • Peer Reviewed
• [Journal Article] Impaired dendritic cells functions disrupt antigen-specific adaptive immune responses in mice with nonalcoholic fatty liver disease. (2010)
  • Author(s): Miyake T, Abe M, et al.
  • Journal Title: J Gastroenterol 45(in press)
  • NAID: 10026610917
  • Peer Reviewed
• [Journal Article] Mechanisms of restoration of immune responses of chronic hepatitis B patients during lamivudine therapy : increased antigen processing and presentation by dendritic cells. (2010)
  • Author(s): Akbar SMF, Abe M, et al.
  • Journal Title: J Viral Hepat 17(in press)
  • Peer Reviewed
• [Presentation] アルコール性肝障害モデルにおける肝樹状細胞の機能 (2010)
  • Author(s): 阿部雅則、濱田麻穂、川崎敬太郎、多田藤政、三宅映己、松浦文三、日浅陽一、恩地森一
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 2010-05-28
• [Presentation] アルコール性肝障害モデルにおける肝樹状細胞の機能 (2010)
  • Author(s): 阿部雅則, 他
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形市
  • Year and Date: 2010-05-28
• [Presentation] HBs抗原+HBc抗原パルス樹状細胞を用いた治療ワクチンの開発 (2010)
  • Author(s): 阿部雅則、ファズレアクバル、恩地森一
  • Organizer: 第96回日本消化器病学会総会
  • Place of Presentation: 新潟
  • Year and Date: 2010-04-22
• [Presentation] エンドトキシンによる肝樹状細胞の低反応性の誘導 (2009)
  • Author(s): 阿部雅則、恩地森一、Angus W.Thomson
  • Organizer: 第13回日本肝臓学会大会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-15
• [Presentation] エンドトキシンによる肝樹状細胞の低反応性の誘導 (2009)
  • Author(s): 阿部雅則
  • Organizer: 第13回日本肝臓学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2009-10-15
• [Presentation] HBs抗原パルスDC投与による肝臓内へのHBs抗原特異的なリンパ球の誘導 (2009)
  • Author(s): 阿部雅則、吉田理、恩地森一
  • Organizer: 第13回日本肝臓学会大会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-14
• [Presentation] 肝形質細胞様樹状細胞は制御性T細胞存在下にアロT細胞に低刺激性を誘導する (2009)
  • Author(s): 時田大輔、阿部雅則、Angus W.Thomson
  • Organizer: 第46回日本消化器免疫学会総会
  • Place of Presentation: 松山
  • Year and Date: 2009-07-23
• [Presentation] 肝樹状細胞の共刺激/共抑制分子が免疫応答に与える影響 (2009)
  • Author(s): 阿部雅則、吉田理、濱田麻穂、道堯浩二郎、堀池典生、日浅陽一、恩地森一
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-05
• [Presentation] TLRリガンドが肝樹状細胞の遊走能に与える影響 (2009)
  • Author(s): 阿部雅則、吉田理、濱田麻穂、三宅映己、多田藤政、日浅陽一、恩地森一
  • Organizer: 第95回日本消化器病学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-05-09
• [Presentation] 肝移植後の免疫抑制剤離脱における樹状細胞と制御性T細胞の役割 (2009)
  • Author(s): 阿部雅則、時田大輔、恩地森一
  • Organizer: 第95回日本消化器病学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-05-08
• [Book] B型肝炎治療の最新戦略HBs抗原+HBc抗原パルス樹状細胞を用いた治療ワクチンの開発 52 (2011)
  • Author(s): 阿部雅則、SMF Akbar、恩地森一
  • Publisher: 消化器科
• [Book] 肝疾患領域の臨床と樹状細胞B型慢性肝炎 58 (2009)
  • Author(s): 阿部雅則、吉田理、恩地森一
  • Publisher: 肝胆膵
• [Book] B型肝炎に対する免疫療法の今後の展望 58 (2009)
  • Author(s): 吉田理、阿部雅則、恩地森一
  • Publisher: 肝胆膵