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炎症性腸疾患感受性遺伝子の同定と機能解析

Research Project

Project/Area Number 18018002
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

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

Principal Investigator

石井 直人  Tohoku University, 大学院・医学系研究科, 准教授 (60291267)

Co-Investigator(Kenkyū-buntansha) 小野 栄夫  東北大学, 大学院・医学系研究科, 教授 (20302218)
木内 喜孝  東北大学, 大学院・医学系研究科, 准教授 (20250780)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 2007: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Keywords炎症性腸疾患 / モデル動物 / 遺伝子連鎖解析 / 遣伝子連鎖解析
Research Abstract

炎症性腸疾患(IBD)は近年急激な患者数の増大が見られる重篤な疾患である。しかしながら、その原因は不明であり有効な治療法も確立されていない。我々がT細胞活性化機構の解析過程で作製した0X40L遺伝子導入マウスはC57BL/6系統依存的にIBDを自然発症する。従って、同マウスはIBD発症責任遺伝子を検索する上で極めて有用な疾患モデルである。既に、感受性系統(C57BL/6)と抵抗性系統(BALB/c)の交配マウス339匹を用いた遺伝子連鎖解析を行い、QTL解析でLod score=7.9と極めて有意なIBD発症関連遺伝子座を特定した。その部位に焦点を当てて解析を進め、同部位の候補遺伝子を70個に絞り、さらに、それら候補遺伝子の中でC57BL/6系統におけるmRNA発現がBALB/cを含む5つの疾患抵抗性系統の発現に比べて5分の1に減弱しているものを見出した。同遺伝子は受容体型タンパク質をコードしており、疾患発症と同遺伝子SNPとの相関が、単点解析(x^2検定)でp=1.2×10^<-8>であった。以上より、同遺伝子発現減少がマウスIBD発症に関与する可能性が示唆された。そこで、同遺伝子の遺伝子導入マウスを作製し、0X40L遺伝子導入マウスと交配した。その結果、同遺伝子の遺伝子導入によりIBD発症が抑制されることが明らかになった。これらの知見は、今回見いだした有力なIBD感受性候補分子が、直接的にIBD発症と関連することを示唆する。

Report

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

    (19 results)

All 2007 2006

All Journal Article (11 results) (of which Peer Reviewed: 6 results) Presentation (8 results)

  • [Journal Article] OX40 ligand in dendritic cells can costimulate NKT and CD4^+ helper T cell antitumor immunity.2007

    • Author(s)
      Zaini, J, et. al.
    • Journal Title

      J. Clin. Invest. 117

      Pages: 3330-3338

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential requirements for OX40 signals on generation of effector and central memory CD4^+ T cells.2007

    • Author(s)
      Soroosh, P., et. al.
    • Journal Title

      J. Immunol. 179

      Pages: 5014-5023

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human CD4^+ central and effector memory T cells produce IL-21: effect on cytokine-driven proliferation of CD4^+ T cell subsets.2007

    • Author(s)
      Onoda, T., et. al.
    • Journal Title

      Int. Immunol. 19

      Pages: 1191-1199

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dendritic cell expression of OX40 ligand acts as a costimulatory, not polarizing, signal for optimal Th2 priming and memory induction in vivo.2007

    • Author(s)
      Jenkins, SJ., et. al.
    • Journal Title

      J. Immunol. 179

      Pages: 3515-3523

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] OX40 costimulation turns off FOXP3^+ T_<REGS・>2007

    • Author(s)
      Vu, MD., et. al.
    • Journal Title

      Blood 110

      Pages: 2511-2519

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of tumor growth and metastasis by depletion of vesicular sorting protein Hrs: its regulatory role on E-Cadherin and β-Catenin.2007

    • Author(s)
      Toyoshima, M., et. al.
    • Journal Title

      Cancer Res. 67

      Pages: 5162-5171

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Important role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice.2007

    • Author(s)
      中野 誠
    • Journal Title

      Circ. Res. 100

      Pages: 662-669

    • Related Report
      2006 Annual Research Report
  • [Journal Article] OX40-OX40L interaction through T cell-T cell contact contributes to CD4 T cell longevity.2006

    • Author(s)
      Pejman Soroosh
    • Journal Title

      J. Immunol. 176

      Pages: 5975-5987

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Important role of endogenous Erythropoietin system to recruit endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice.2006

    • Author(s)
      佐藤 公雄
    • Journal Title

      Circulation 113

      Pages: 1442-1450

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Regulatory T cell-like activity of Foxp3^+ adult T-cell leukemia cells.2006

    • Author(s)
      陳書明
    • Journal Title

      Int. Immunol 18

      Pages: 269-277

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A signal adaptor SLAM-associated protein regulates spontaneous autoimmunity and Fas-dependent lymphoproliferation in MRL-Fas^<lpr> lupus mice.2006

    • Author(s)
      Komori, H
    • Journal Title

      J. Immunol. 176

      Pages: 395-400

    • Related Report
      2006 Annual Research Report
  • [Presentation] STAM1/2 double knockout mice enhance inflammatory reaction.2007

    • Author(s)
      井草龍太郎
    • Organizer
      第37回日本免疫学会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] OX40-OX40L Interactions Determine the Size of Memory CD8+ T cell pools against Listeria Infection2007

    • Author(s)
      Mousavi, SF, et. al.
    • Organizer
      第37回日本免疫学会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] BTLA,HVEMに対するモノクローナル抗体の作製2007

    • Author(s)
      青木淳
    • Organizer
      第37回日本免疫学会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] Characterization of human lymphocytes in humanized NOG mice2007

    • Author(s)
      渡邊庸平
    • Organizer
      第37回日本免疫学会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] Regulation of MHC class II function by ESCRT proteins, STAM1/2Regulation of MHC class II function by ESCRT proteins, STAM1/2.2007

    • Author(s)
      村田和子
    • Organizer
      第37回日本免疫学会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-20
    • Related Report
      2007 Annual Research Report
  • [Presentation] Co-inhibitory roles for Glucocorticoid-induced TNF receptor (GITR) in CD ld-dependent natural killer T cells.2007

    • Author(s)
      陳書明
    • Organizer
      第37回日本免疫学会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-20
    • Related Report
      2007 Annual Research Report
  • [Presentation] Characterization of human lymphocytes in humanized NOG mice2007

    • Author(s)
      渡邊庸平
    • Organizer
      第61回日本細菌学会東北支部総会
    • Place of Presentation
      仙台
    • Year and Date
      2007-08-23
    • Related Report
      2007 Annual Research Report
  • [Presentation] OX40-OX40L Interactions Determine the Size of Memory CD8+ T cell pools against Listeria Infection2007

    • Author(s)
      Mousavi, SF., et. al.
    • Organizer
      第61回日本細菌学会東北支部総会
    • Place of Presentation
      仙台
    • Year and Date
      2007-08-23
    • Related Report
      2007 Annual Research Report

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

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