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Th1免疫応答促進による抗腫瘍免疫反応増強

Research Project

Project/Area Number 18015003
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHokkaido University

Principal Investigator

小野江 和則  Hokkaido University, 遺伝子病制御研究所, 教授 (40002117)

Co-Investigator(Kenkyū-buntansha) 岩渕 和也  北海道大学, 遺伝子病制御研究所, 准教授 (20184898)
柳川 芳毅  北海道大学, 遺伝子病制御研究所, 助教 (20322852)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2007: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2006: ¥5,700,000 (Direct Cost: ¥5,700,000)
Keywords樹状細胞 / NK-T細胞 / ネガティブフィードバック / サイトカイン / 抗腫瘍免疫 / GSK-3 / α-GalCer / メタボリックシンドローム / IL-21 / CpG
Research Abstract

自然免疫と獲得免疫をつなぐNK-T細胞は、大量のサイトカインを産生することにより獲得免疫の質,量を制御する。従って、NK-T細胞の産生するサイトカインをコントロールできれば、その後の免疫応答を選択できる。
本年度では、NK-T細胞の機能を詳細に解析するため、NK-Tハイブリドーマを作成した。作成したNK-Tハイブリドーマは、通常のNK-T細胞と同様の反応性を示すことが判明し、このハイブリドーマを用いることにより、抗原提示細胞側の機能修飾解析などが可能となった。次に、NK-T細胞を刺激する樹状細胞(DC)の機能を修飾する方法として、glycogen synthase kinase 3 (GSK3) の影響を検討し、GSK3はTh2型の反応をDCに誘導することを発見した。また、DC上のMHCクラスIによって、NK-T細胞のサイトカイン産生能がTh2側にシフトすることも明らかにした。これまでIL-21が抗腫瘍活性を増加させると報告されてきたが、今回このメカニズムとして、IL-21処理DCがNK-T細胞からのIFN-γ産生を増強することを明らかにした。また、DCの産生するTNF-αとIL-10に関与するシグナル伝達系の違いについても明らかにし、報告した。一方、前Bリンパ球系腫瘍を自然発症すSL/Khマウスにおいて、NK-T細胞の分化異常を証明した。
近年、我国ではメタボ対策が強調されている。我々は、メタボマウスにおいては、NK-T細胞を介する免疫制御の結果、IFN-γ産生が低下してTh1型の細胞性免疫反応が低下することを明らかにした。この研究結果は、動脈硬化食を摂取したマウスとは逆の関係を示した。これらの違いの原因として関与するNK-T細胞サブセットの違いを示唆するデータを得た。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (49 results)

All 2008 2007 2006

All Journal Article (38 results) (of which Peer Reviewed: 20 results) Presentation (4 results) Book (7 results)

  • [Journal Article] H2-Dd-mediated upregulation of IL-4 production by natural killer T cell and dendritic cell interaction.2008

    • Author(s)
      Mizuuchi, K.
    • Journal Title

      Immunology 124

      Pages: 102-111

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Allograft inflammatory factor-1 augments macrophage phagocytotiic activity and accelerates the progression of atherosclerosis in ApoE-7-mice.2008

    • Author(s)
      Mishima, T.
    • Journal Title

      Int. J. Mol. Med. 21

      Pages: 181-187

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-inflammatory effect of angiotensin type I receptor antagonist on endotoxin-induced uveitis in rats.2008

    • Author(s)
      Miyazaki, A.
    • Journal Title

      GraefbsArch. Clin. Exp. Ophthalmol. 246

      Pages: 754-757

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effct of high fat diet on NKT cell function and NKT cell-mediated regulation of Thl resonses.2008

    • Author(s)
      Miyazaki, Y.
    • Journal Title

      Scand. J. Immunol. 67

      Pages: 230-237

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective syllergy in anti-inflammatory cytokine production upon cooperated signaling via TLR4 and TLR2 in murine conventlonal dendritic cells.2008

    • Author(s)
      Hlrata, N.
    • Journal Title

      Mol. Immunol. 45

      Pages: 2734-2742

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expansion of CD+4CD28-T cells producing high levels of interferon-γ in peripheral blood of patients with multiples sclerosis.2008

    • Author(s)
      Miyazaki, Y.
    • Journal Title

      Multiple Sclerosis Journal. 14

      Pages: 1044-1055

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro induction of natural killer T cells from embryonic stem cells prepared by somatic cell nucleart ransfer.2008

    • Author(s)
      wakao, H.
    • Journal Title

      FASEB J 22

      Pages: 2223-2231

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse.2008

    • Author(s)
      Ohnishi, N.
    • Journal Title

      Proc. Natl. Acad. Sci. USA 105

      Pages: 1003-1008

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Th2飽細胞誘導樹状細胞の分化とglycogen synthase kinase 3.2008

    • Author(s)
      小野武紀
    • Journal Title

      臨床免疫・アレルギー科 50

      Pages: 17-24

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of NKT-cell hybridomas expressing invariant T-cell antigen receptors.2007

    • Author(s)
      NyambayaL, D.
    • Journal Title

      J. Clin. Exp. Hematopathol. 47

      Pages: 1-8

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thl or Th2 balance regulated by interaction between dendritic cells and NKT cells.2007

    • Author(s)
      Onoe, K.
    • Journal Title

      Immunol, Res. 38

      Pages: 319-332

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis in mice.2007

    • Author(s)
      Kitamei, H.
    • Journal Title

      Immunobiology 212

      Pages: 11-18

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteopontin aggravates experimental autoimmune uveoretinitis in mice.2007

    • Author(s)
      Kitamura, M.
    • Journal Title

      J. Immunol. 178

      Pages: 6567-6572

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-21 enhances dendritic cell ability to induce interfbron-γ production by natural killer Tcells.2007

    • Author(s)
      Maeda, M.
    • Journal Title

      Immunobiology. 212

      Pages: 537-547

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced IL-10 production by TLR4 and TLR2 primed dendritic cell supon TLR restimulation,2007

    • Author(s)
      Yanagawa, Y.
    • Journal Title

      J. Immunol. 178

      Pages: 6173-6180

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glycogen synthase kinase 3 activity during development of bone marrow-derived dendritic cells (DC) essentlal for the DC function to induce T helper 2 polarization.2007

    • Author(s)
      Ono, T
    • Journal Title

      Immunology 122

      Pages: 189-198

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Administration of high-dose intact immunoglobulin has an anti-resorption effbct in a mouse model of reproductive failure.2007

    • Author(s)
      Takeda, M.
    • Journal Title

      Mol. Human Reprod. 13

      Pages: 807-814

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] オステオポンチンの自己免疫疾患発症への関与.2007

    • Author(s)
      北村瑞
    • Journal Title

      臨床免疫・アレルギー科 47

      Pages: 285-289

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] L-21による樹状細胞機能の修飾.2007

    • Author(s)
      柳川芳毅
    • Journal Title

      臨床免疫・アレルギー科 48

      Pages: 243-249

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CpG反応樹状細胞によるNKT細胞からのIL-4産生誘導.2007

    • Author(s)
      水内一臣
    • Journal Title

      臨床免疫・アレルギー科 48

      Pages: 236-242

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of NKT-cell hybridomas expressing invariant T-cell antigen receptors.2007

    • Author(s)
      Nyambayar, D.
    • Journal Title

      J. Clin. Exp. Hematopathol. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Th1 or Th2 balance regulated by interaction between dendritic cells and NKT cells.2007

    • Author(s)
      Onoe, K.
    • Journal Title

      Immunol. Res. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis in mice.2007

    • Author(s)
      Kitamei, H.
    • Journal Title

      Immunobiology (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Osteopontin aggravates experimental autoimmune uveoretinitis in mice.2007

    • Author(s)
      Kitamura, M.
    • Journal Title

      J. Immunol. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Enhanced IL-10 production by TLR4 and TLR2 primed dendritic cells upon TLR resimulation.2007

    • Author(s)
      Yanagawa, Y.
    • Journal Title

      J. Immunol. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Glycogen synthase kinase 3 activity during development of bone marrow-derived dendritic cells (DC) essential for the DC function to induce T helper 2 polarization.2007

    • Author(s)
      Ono, T.
    • Journal Title

      Immunology (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] IL-21 enhances dendritic cell ability to induce interferon-γ production by natural killer T cells.2007

    • Author(s)
      Maeda, M.
    • Journal Title

      Immunobiology (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Low-dose lipopolysaccharide modifies the production of IL-12 by dendritic cells in response to various cytokines.2006

    • Author(s)
      Saito, Y.
    • Journal Title

      J. Clin. Exp. Hematopathol. 46

      Pages: 31-36

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distinct regulation of CD40-mediated interleukin (IL)-6 and IL-12 production via mitogen-activated protein kinase (MAPK) and nuclear factor κ B-inducing kinase (NIK) in mature dendritic cells.2006

    • Author(s)
      Yanagawa, Y.
    • Journal Title

      Immunology 117

      Pages: 526-535

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Influence of EPIYA-repeat polymorphism on the phosphorylation-dependent biological activity of Helicobacter Pylori CagA.2006

    • Author(s)
      Naito, M.
    • Journal Title

      Gastroenterology 130

      Pages: 1181-1190

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of blue honeysuckle (Lonicera caerulea L.) extract on lipopolysaccharide-induced inflammation in vitro and in vivo.2006

    • Author(s)
      Jin, X.H.
    • Journal Title

      Exp. Eye Res. 82(5)

      Pages: 860-867

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Granulocytapheresis in patients with refractory ocular Behcet's disease.2006

    • Author(s)
      Namba, K.
    • Journal Title

      J. Clin. Apheresis. 21

      Pages: 121-128

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of nuclear factor κ B (NF- κ B), pyrrolidine dithiocarbamate.2006

    • Author(s)
      Kitamei, H.
    • Journal Title

      J. Leukoc. Biol. 79

      Pages: 1193-1201

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Natural killer T cells ameliorate antibody-induced arthritis in macrophage migration inhibitory factor transgenic mice.2006

    • Author(s)
      Takagi, D.
    • Journal Title

      Int. J. Mol. Med. 18

      Pages: 829-836

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Natural killer, natural killer T, helper and cytotoxic T cells in the decidua from sporadic miscarriage.2006

    • Author(s)
      Shimada, S.
    • Journal Title

      Am. J. Reprod. Immunol. 56

      Pages: 193-200

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pro-oxidative diesel exhaust particle chemicals inhibit LPS-induced dendritic cell responses involved in T-helper differentiation.2006

    • Author(s)
      Chan, C-F.R.
    • Journal Title

      J. Allergy Clin. Immunol. 118

      Pages: 455-465

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Lower prevalence of circulating natural killer T cells in patients with angina : a potential novel marker for coronary artery disease.2006

    • Author(s)
      Andoh, Y.
    • Journal Title

      Coron. Artery Dis. 17

      Pages: 523-528

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effect of T helper 1 (Th1)/Th2 cytokine on chemokine-induced dendritic cell functions.2006

    • Author(s)
      Clingan, J.M.
    • Journal Title

      Cell. Immunol. 242

      Pages: 72-79

    • Related Report
      2006 Annual Research Report
  • [Presentation] Glycogen synthase kinase 3 activity during development of bone marrow-derived dendritic cells (DC) essential for the DC function to induceT heler 201 polarization.2007

    • Author(s)
      Ono, T.
    • Organizer
      第37回日本免疫学会学術集会
    • Place of Presentation
      東京グランドブリンスホテル新高輪
    • Year and Date
      2007-11-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] Enhanced IL-10 production by TLR4 and TLR2 primed dendritic cellsupon TLRr estimulation.2007

    • Author(s)
      Yanagawa, Y.
    • Organizer
      第37回日本免疫学会学術集会
    • Place of Presentation
      東京グランドブリンスホテル新高輪
    • Year and Date
      2007-11-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] 特別講演:Thl or Th2 balance regulated by interaction between dendriticcells and NKT cells.2007

    • Author(s)
      小野江和則
    • Organizer
      第92回北海道癌談話会
    • Place of Presentation
      札幌北海道大学医学部第2講堂
    • Year and Date
      2007-09-08
    • Related Report
      2007 Annual Research Report
  • [Presentation] 特別講演:NKT細胞の機能と炎症・免役制御.2007

    • Author(s)
      岩渕和也
    • Organizer
      第6回MSワークショップ
    • Place of Presentation
      札幌札幌プリンスホテル
    • Year and Date
      2007-08-04
    • Related Report
      2007 Annual Research Report
  • [Book] (監修) 医科免疫学2008

    • Author(s)
      小野江和則
    • Total Pages
      470
    • Publisher
      南江堂
    • Related Report
      2007 Annual Research Report
  • [Book] 分子細胞生物学辞典 (第2版)2008

    • Author(s)
      小野江和則
    • Total Pages
      1184
    • Publisher
      東京科学同人
    • Related Report
      2007 Annual Research Report
  • [Book] バイオとナノの融合 II 新生命科学の応用北海道大学COE研究成果編集委員会 編2007

    • Author(s)
      小野江和則
    • Total Pages
      18
    • Publisher
      北海道大学出版会
    • Related Report
      2007 Annual Research Report
  • [Book] 生化学辞典 (第4版)2007

    • Author(s)
      小野江和則
    • Total Pages
      1616
    • Publisher
      東京科学同人
    • Related Report
      2007 Annual Research Report
  • [Book] 医科免疫学2007

    • Author(s)
      小野江和則
    • Publisher
      南江堂(印刷中)
    • Related Report
      2006 Annual Research Report
  • [Book] ペプチド抗原と脂質を認識する二つのT細胞系.2007

    • Author(s)
      小野江和則
    • Publisher
      COEバイオとナノ(印刷中)
    • Related Report
      2006 Annual Research Report
  • [Book] メディカル免疫学,Really Essential Medical Immunology, by Ivan Roitt & Arthur Rabson.2006

    • Author(s)
      小野江和則
    • Total Pages
      96
    • Publisher
      西村書店
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2018-03-28  

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