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Analysis of the CD47-SHPS-1 signaling system in autoimmune disease

Research Project

Project/Area Number 18591098
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionGunma University

Principal Investigator

KANEKO Yoriaki  Gunma University, Graduate School of Medicine, Assistant Professor (00334095)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsSHPS-1 / CD47 / ITIM / macrophage / dendritic cells / NKT / autoimmunity / 実験的自己免疫性脳脊髄炎 / Th-17 / NKT細胞 / α-GalCer / 肺転移
Research Abstract

Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1), which is originally identified as a substrate for protein tyrosine phosphatases SHP-1 and SHP-2, is a member of immunoglobulin superfamily. SHPS-1 contains ITIM in its intracellular domain and its extra-cellular region interacts with CD47, which is widely expressed on immune cells. The interaction between CD47 and SHPS-1 constitutes a cell-cell communication system (the CD47-SHPS-1 signaling system) that may function in regulation of a variety of biological responses. SHPS-1 is predominantly exposed on macrophages and dendritic cells (DCs), and the CD47-SHPS-1 signaling system is considered to be a negative regulator of immune responses. We investigated the physiological roles of SHPS-1 by the use of SHPS-1 mutant mice, which lack most of the cytoplasmic region of its protein and we revealed some important functions. SHPS-1 negatively regulates the phagocytosis of RBCs by splenic macrophages and it determines both the lifespan of individual RBCs and the number of circulating erythrocytes. SHPS-1 on DCs is essential for both priming of naive T cells and the activation of NKT cells. SHPS-1 positively regulates the development of autoimmune disease and α-GalCer-induced anti-metastatic activities. These results indicate the CD47-SHPS-1 signaling system plays important roles in immune responses.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (15 results)

All 2007

All Journal Article (10 results) (of which Peer Reviewed: 5 results) Presentation (5 results)

  • [Journal Article] Enhanced phagocytosis of CD47-deficient red blood cells by splenic macrophages requires SHPS-12007

    • Author(s)
      Ishikawa-Sekigami T, et. al.
    • Journal Title

      Biochem Biophys Res Commun 343

      Pages: 1197-1200

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Regulation by Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate-1 of α-Galactosylceramide-Induced Antimetastatic Activity and Th1 and Th2 Responses of NKT Cells.2007

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

      J Immunol 178

      Pages: 6164-72

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Resistance to experimental autoimmune encephalomyelitis and impaired T cell priming by dendritic cells in SRC homology 2 domain-containing protein tyrosin phosphatase substrate-1 mutant mice.2007

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

      J Immunol 179

      Pages: 869-77

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Enhanced phagocytosis of CD47-deficient red blood cells by spienic macrophages requires SHPS-12007

    • Author(s)
      Ishikawa-Sekigami T, Kaneko Y, et. al.
    • Journal Title

      Biochem Biophys Res Commun 343(4)

      Pages: 1197-1200

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Regulation by Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate-1 of α-Galactosylceramide-Induced Antimetastatic Activity and Th1 andTh2 Responses of NKT Cells2007

    • Author(s)
      Okaj o J, Kaneko Y, et. al.
    • Journal Title

      J Immunol 178(10)

      Pages: 6164-72

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Resistance to experimental autoimmune encephalomyelitis and impaired T cell priming by dendritic cells in SRC homology 2 domain-containing protein tyrosin phosphatase substrate-1 mutant mice2007

    • Author(s)
      Tomizawa T, Kaneko Y, et. al.
    • Journal Title

      J Immunol 179(2)

      Pages: 867-77

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Resistance to experimental autoimmune encephalomyelitis and impaired T cell priming by dendritic cells in SRC homology 2 domain-containing protein tyrosin phoshatase substrate-1 mutant mice2007

    • Author(s)
      Tomizawa T, Kaneko Y, et. al.
    • Journal Title

      Joumal of Immunology 179

      Pages: 869-877

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation by Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate-1 of α-Galactosylcerarnide-lnduced Antimetastatic Activity and Thl and Th2 Resonses of NKT Cells2007

    • Author(s)
      Okajo J, Kaneko Y, et. al.
    • Journal Title

      Jounal of Immunology 178

      Pages: 6164-6172

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced phagocytosis of CD47-deficient red blood cells by splenic macrophages requires SHPS-12007

    • Author(s)
      Ishikawa-SekigamiT, KanekoY, MatozakiT. et al.
    • Journal Title

      Biochem Biophys Res Commun. 343・4

      Pages: 1197-1120

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Regulation by SHPS-1 of α-GalCer-induced Antimetastatic Activity and Th1 and Th2 Responses of Natural Killer T Cells2007

    • Author(s)
      Okajo J, Kaneko Y, Nojima Y et al.
    • Journal Title

      J Immunol. (in press)

    • Related Report
      2006 Annual Research Report
  • [Presentation] Resistance to Experimental Autoimmune Encephalomyelitis and Impaired T cell Priming by Dendritic Cells in SHPS-1 Mutant Mice2007

    • Author(s)
      金子和光 他
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Resistance to Experimental Autoimmune Encephalomyelitis and Impaired T cell Priming by Dendritic Cells in SHPS-1 Mutant Mice2007

    • Author(s)
      Kaneko Y, et. al.
    • Organizer
      The 38th Annual Meeting of the Japanese Society of Immunology
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-11-22
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Resistance to Experimental Autoimniune Encephalomyelitis and Impaired T cell Priming by Dendritic Cells in SHPS-1 Mutant Mice2007

    • Author(s)
      金子 和光, 他
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] 自己免疫性関節炎におけるSHPS-1の機能解析2007

    • Author(s)
      奥沢千絵、金子和光 他
    • Organizer
      日本臨床免疫学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-10-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Resistance to collagen-induced arthritis in SHPS-1 mutant mice2007

    • Author(s)
      Okuzawa C, et. al.
    • Organizer
      The 35th Annual Meeting of the Japan Society for Clinical Immunology
    • Place of Presentation
      Osaka
    • Year and Date
      2007-10-19
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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