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Fc受容体を介したIgE,IgGによるマスト細胞機能の調節

Research Project

Project/Area Number 12139201
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

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

Principal Investigator

高井 俊行  東北大学, 加齢医学研究所, 教授 (20187917)

Co-Investigator(Kenkyū-buntansha) 中村 晃  東北大学, 加齢医学研究所, 助手 (20344723)
Project Period (FY) 2000 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥34,200,000 (Direct Cost: ¥34,200,000)
Fiscal Year 2003: ¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2002: ¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2001: ¥10,200,000 (Direct Cost: ¥10,200,000)
Keywordsallergy / PIR-B / mast cell / MHC class I / transplantation / GVHD / inhibitory receptor / Th2 response / dendritic cell / Fcレセプター / PIR / アレルギー / アナフィラキシー / ヒスタミン / マスト細胞 / 自己免疫疾患
Research Abstract

Immunoglobulin(Ig)-like receptor(IgLR)という範疇に属する新規なレセプター分子群が続々と単離され,その機能が注目され始めてまだ5年ほどしか経過していないが,これらが免疫調節に重要な役割を担う証拠が次々と挙がっている.マウスのPaired IgLR(PIR)は活性化シグナルを伝達するPIR-Aと,逆に抑制性シグナルを伝達するPIR-Bのペアからなる代表的なIgLRであるが,PIR-Bが欠損するとB細胞,樹状細胞のシグナル伝達が撹乱され,その免疫応答はTh2型に著しく偏ることを我々は本研究課題において示してきた.本年度は,正常な免疫応答に不可欠であるこのレセプター・ペアが何を認識し,どのようなシグナルを細胞内に導入しているのか,さらに免疫疾患にどのように関連しているのかを明らかにすることでマスト細胞機能,およびアレルギーや自己免疫などの発症に関する新規な機構を解明することを目的とした.その縞果,PIR-B,PIR-AともにMHC class I分子を認識し,PTR-Bの欠損によって移植片対宿主反応が亢進してホストのGVHDが増悪することが分かった,さらにマスト細胞はこの識別機構を喪失した結果,刺激感受性が増大し,アレルギーを発症しやすくなる素地を形成することが分かった.したがってPIRはTCRやKIRとともに自己MHC class Iを認識する第3のシステムを構築し,自己反応性および外界からの無用な刺激応答性を回避していることが示唆された.

Report

(4 results)
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Kaifu T et al.: "Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice."J.Clin.Invest.. 111(3). 323-332 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Koga T et al.: "ITAM-mediated costimulatory signals cooperate with RANKL for bone homeostasis."Nature. (in press.). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamaguchi A et al.: "Possible role of autoantibody in the pathophysiology of GM2 angliosidoses."J.Clin.Invest.. 113(2). 200-208 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakamura A et al.: "Exacerbated graft-versus-host disease in Pirb^<-/-> mice."Nature Immunology. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakamura, A., et al.: "Deregulation of peripheral B cell development in enhanced severity of collagen-induced arthritis in FcγRIIB-deficient mice"J Autoimmu. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yajima K, et al.: "FcγRIIB deficiency with Fas mutation is sufficient for the development of systemic autoimmune disease"Eur.J.Immunol. 33. 1020-1029 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akiyama K, et al.: "Targeting of apoptotic tumor cells to Fcγ receptors provides efficient and versatile vaccination against tumors by dendritic cells"J.Immunol. 170(4). 1641-1648 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kaifu, T., et al.: "Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice"J.Clin.Invest. 111(3). 323-332 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ujike, A., et al.: "Impaired dendritic cell maturation and increased T_H2 responses in PIR-B^<-/-> mice"Nature Immunol. 3. 542-548 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takai T.: "Roles of Fc receptors in autoimmunity"Nature Rev. Immunol. 2. 580-592 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ujike et al.: "Hypersensitive B cells and Th2-prone immune responses in Paired Immunoglobulin-like Receptor (PIR)-B-deficient mice"(投稿中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Kato et al.: "FcγyRIIB negatively regulates the pre-BCR signaling for apoptosis"J. Immunol.. 168. 629-634 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kubo et al.: "Drastic up-regulation of FcεRI on mast cells is induced by IgE binding through stabilization and accumulation of FcεRI on the cell"J. Immunol.. 167. 3427-3434 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kaji et al.: "Functional association of CD9 molecule with FcγIII receptor in macrophages"J. Immunol.. 166. 3256-3265 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yuasa et al.: "Lyn is essential for Fcγ receptor III-mediated systemic anaphylaxis but not for the Arthus reaction"J. Exp. Med.. 193. 563-572 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 1.Yuasa,T., et al: "Lyn is essential for Fcγ receptor III-mediated systemic anaphylaxis but not for the Arthus reaction."J.Exp.Med.. 193. 563-572 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 2.Lee,K.H., et al.: "Stimulatory function of gp49A, a murine Ig-like receptor, in RBL-2H3 cells."J.Immunol.. 165. 4970-4977 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 3.Yoneto,T.,et al.: "A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage Plasmodium berghei XAT infection."J.Immunol.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 4.Kaji,K., et al.: "Functional association of CD9 molecule with FCγIII receptor in macrophages."J.Immunol.. 166. 3256-3265 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 5.Ohah DN, et al.: "Mucosal defence against gastrointestinal nematodes : Responses of mucosal mast cells and mouse mast cell protease 1 during primary Strongyloides venezuelensis infection in FcRγ-knockout mice"Infect.Immun.. 68. 4968-4971 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 6.Wakayama,H., et al.: "Abolition of anti-glomerular basement membrane antibody-mediated glomerulonephritis in FcRγ-deficient mice."Eur.J.Immunol.. 30. 1182-1190 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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