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Apoptosis signals in autoimmune disease

Research Project

Project/Area Number 13670453
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

KISHI Hiroyuki  Toyama Medical and Pharmaceutical University Faculty of Medeicine Associate Professor, 医学部, 助教授 (60186210)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsapoptosis / T-lymphocyte / T cell receptor / MAP kinase / Bax / mitochondria / microsome / caspase activated DNase / T細胞抗原受容体 / 胸腺細胞 / p38MAPキナーゼ
Research Abstract

It is supposed that the auto-reactive T cells are involved in the development of autoimmune diseases. Auto-reactive T cells are usually eliminated from the host by apoptosis that is induced through TCR-signals in the thymus or in the periphery. Dysfunction of the immune surveillance system leads to appearance of auto-reactive T cells in the periphery. In this study, we investigated the TCR signals that induce apoptosis in thymocytes or T cells to unravel the mechanism of the development of autoimmune diseases. First, we analyzed the role of mitochondria in TCR-induced apoptosis of thymocytes and showed that activated p38 kinase pathway by TCR-stimulation induces translocation of Bax to mitochondria, causing DYm-disruption, and the release of cytochrome c, which finally induces caspase-3-mediated apoptosis in thymocytes. Second, we investigated the localization and the function of caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD), which play a central role in chromatin fragmentation in apoptotic cells, in thymocytes prior or post in vivo TCR-stimulation. We showed that TCR-engagement of thymocytes induced caspase-3-dependent activation of CAD localized not only in cytosol but also in microsome, leading to their translocation to nuclei and the resulting DNA fragmentation in harmony. These results will prompt us to analyze the TCR-induced apoptosis signals in T cells from patients of autoimmune diseases.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Yoshino T et al.: "Differential involvement of p38 MAP kinase pathway and Bax translocation in the mitochondria-mediated cell death in TCR-and dexamethasone-stimulated thymocytes"European Journal of Immunology. 31. 2702-2708 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagata T et al.: "The regulation of DNAse activities in subcellular compartments of activated thyocytes"Immunology. 105. 399-406 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshino T et al.: "Differential involvement of p38 MAP kinase pathway and Bax translocation in the mitochondria-mediated cell death in TCR- and dexamethasone-stimulated thymocytes"European Journal of Immunology. 105. 399-406 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagata T et al.: "The regulation of DNAse activities in subcellular compartments of activated thymocytes."Immunology. 105. 399-406 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagata T, et al.: "The regulation of DNAse activities in subcellular compartments of activated thymocytes"Immunology. 105. 399-406 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Yoshino: "Differential involvement of p38 MAP kinase pathway and Bax translocation in the mitochondria-mediated cell death in TCR-and dexamethasone-stimulated thymocytes"European Journal of Immunology. 31. 2702-2708 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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