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Role of inducible costimulator (ICOS) in the development of an autoimmune disease

Research Project

Project/Area Number 15591056
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 InstitutionSaga University (2004)
佐賀医科大学 (2003)

Principal Investigator

TADA Yoshifumi  Saga Medical School, Internal Medicine, Assistant professor, 医学部, 講師 (70284627)

Co-Investigator(Kenkyū-buntansha) NAGASAWA Kohei  Saga Medical School, Internal Medicine, professor, 医学部, 教授 (00108721)
KOARADA Syuichi  Saga Medical School, Internal Medicine, Assistant professor, 医学部, 助手 (50304887)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsinducible costimulator / costimulatory molecule / autoimmunity / autoantibody / nephritis / lupus
Research Abstract

1.Generation of icos-deficient MRL/lpr mice
Icos-deficient mice were backcrossed into MRL/lpr mice for seven generations. Icos +/- mice were intercrossed, and icos+/+ MRL/lpr and icos-/- MRL/lpr mice were generated.
2.Lymphoproliferation and splenomegaly
Icos-/-MRL/lpr mice showed less severe lymphadenopathy, but similar level of splenomegaly as compared with those in icos+/+ MRL/lpr mice.
3.Analysis of spleen cells
In the spleen from iocs-/- MRL/lpr mice, B220-T cells and CD4+ T cells were reduced as compared with that from control MRL/lpr mice. Regarding splenic CD4+ T cells, the reduction of memory T cells and B22O-CD4+ T cells were noted in icos-/- MRL/lpr mice. The intracellular cytokine staining of CD4+ T cells showed that the ratio of IFN-gamma-positive calls/IL-4-positive cell was decreased in icos-/- MRL/ipr mice. The result indicates that in CD4+ T cells from icos-/- MRL/lpr mice, cytokine balance is biased to Th2 as compared with that in icos+/+ MRLlpr mice
4.Autoantibodies
In icos-/- MRL/lpr mice, serum anti-dsDNA antibody levels of IgG1,IgG2a,and IgM subclasses, but not IgG3 subclass were decreased as compared with those in icos+/+ MRL/lpr mice.
5.Cytokine levels
In icos-/- MRL/lpr mice, serum levels of MCP-1 and IL-12p70 were lower than those in icos+/+ MRL/lpr mice.
6.Glomerulonephritis
The severity of glomerulonephritis was not different between icos-/- MRL/lpr mice and icos+/+ MRL/lpr mice. However, perivascular and interstitial infiltration of inflammatory cells was completely abolished in icos-/- MRL/lpr mice.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (3 results)

All 2003

All Journal Article (3 results)

  • [Journal Article] Acceleration of the onset of collagen-induced arthritis by a deficiency of platelet endothelial cell adhesion molecule 12003

    • Author(s)
      Yoshidfumi Tada, et al.
    • Journal Title

      Arthritis and Rheumatism 48

      Pages: 3280-3290

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Acceleration of the onset of collagen-induced arthritis by a deficiency of Platelet endothelial cell adhesion molecule 12003

    • Author(s)
      Yoshifumi Tada, et al.
    • Journal Title

      Arthritis and Rheumatism 48

      Pages: 3280-3290

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Acceleration of the onset of collagen-induced arthritis by a deficiency of platelet endothelial cell adhesion molecule 1.2003

    • Author(s)
      Yoshidfumi Tada, et al.
    • Journal Title

      Arthritis and Rheumatism 48

      Pages: 3280-3290

    • Related Report
      2004 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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