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The development of an innovative therapy for autoimmune diseases by controlling transcription factors in the regulatory T cells.

Research Project

Project/Area Number 15591050
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 InstitutionThe University of Tokyo

Principal Investigator

YOSHIKATA Misaki  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (60219615)

Co-Investigator(Kenkyū-buntansha) KAWAHATA Kimito  The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (70334406)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsregulatory T cells / transcription factors / autoimmune diseases / FOXP3 / SOCS3 / 転写因子 / 分化誘導 / cDNAクローニング / レトロウイルスベクター / トランスジェニックマウス / ホメオスタシス
Research Abstract

Cb4(+)CD25(+)regulatory T cells (Treg) contributes in homeostasis of the immune system by controlling an immune response. Recent accumulated findings suggest naturally occurring CD4(+)CD25(+)regulatory T cells which develop at least in the thymus via autoreactivity positive selection consists of an distinct T cell subset. As it is known that transcription factors contribute in the determination of cell lineage and transduction of the transcription factors induces cell differentiation. In order to find Treg-specific transcription factors, we generated Treg-specific expression cDNA library by subtraction. Among the library, we found two factors ; the one is (189), and the other is FOXP3. Foxp3 is demonstrated to play a pivotal role in Treg development. Therefore, we subsequently extended our research to screen FOXP3-assocaited molecules. By two yeast hybrid, we found SOCS3 is associated with FOXP3. The association involves SH2 region of SOCS3 and 81-210 amino acids region of FOXP3. Furthermore, We found that FOXP3 is associated the endogenous SOCS3 in FOXP3-transfected Treg cell clone. Considering the role of SOCS3 in the signal transduction, it is of interest to imagine that SOCS3 contribute in the immune regulation via Treg development.

Report

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

    (15 results)

All 2004 2003 Other

All Journal Article (12 results) Publications (3 results)

  • [Journal Article] Chondromodulin-I, a cartilage-derived angiogenesis inhibitory factor, suppresses T cell response2004

    • Author(s)
      Setoguchi K, Misaki Y et al.
    • Journal Title

      Arthritis & Rheumatism 50

      Pages: 828-839

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] T cell accumulating in the inflamed joints of a spontaneous murine model of rheumoid arthritis become restricted to common clonotypes during disease progression2004

    • Author(s)
      Kobari Y, Misaki Y et al.
    • Journal Title

      International Immunology 16

      Pages: 131-138

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chondromodulin-I, a cartilage-derived angiogenesis inhibitory factor, suppresses T cell response ; an implication of a therapeutic potential for the treatment of arthritis.2004

    • Author(s)
      Setoguchi K, Misaki Y, Kawahata K, Shimada, K Takuo J, Tanaka S, Oda H, Chisa Shukunami C, Nishizaki Y, Hiraki Y, Yamamoto K.
    • Journal Title

      Arthritis & Rheumatism. 50(3)

      Pages: 828-839

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] T cells accumulating in the inflamed joints of a spontaneous murine model of rheumatoid arthritis become restricted to common clonotypes during disease progression.2004

    • Author(s)
      Kobari Y, Misaki Y, Setoguchi K, Zhao W, Komagata Y, Kawahata K, Iwakura Y, Yamamoto K.
    • Journal Title

      International Immunology 16(1)

      Pages: 131-138

    • NAID

      10013082886

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chondromodulin-I, a cartilage-derived angiogenesis inhibitory factor, suppresses T cell respose.2004

    • Author(s)
      Setoguchi K, Misaki Y et ai.
    • Journal Title

      Arthritis & Rheumatism 50

      Pages: 828-839

    • Related Report
      2004 Annual Research Report
  • [Journal Article] T cells accumulating in the inflamed joints of a spontaneous murine model of rheumatoid arthritis become restricted to common clonotypes during disease progession.2004

    • Author(s)
      Kobari Y, Misaki Y et al.
    • Journal Title

      International Immunology 16

      Pages: 131-138

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Systemic lupus erythematosus and thrombotic thrombocytopenic2003

    • Author(s)
      Hamasaki K, Kanda H, Misaki Y et al.
    • Journal Title

      Clin.Rheumatology 22

      Pages: 355-358

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Reconstitution of CD8 T cells by retroviral transfer of TCR αβ-chain genes isolated from a colonally expanded P815-infiltrating lymphocyte2003

    • Author(s)
      Tahara H, Misaki Y, Yamamoto K et al.
    • Journal Title

      J Immunology 171

      Pages: 2154-2160

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Evaluation of functional disability using the health assessment questionnaire Japanese Patients with Systemic Sclerosis2003

    • Author(s)
      Kuwana M, Sato S, Misaki Y et al.
    • Journal Title

      J.Rheumatology 30

      Pages: 1253-1258

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Systemic lupus erythematosus and thrombotic thrombocytopenic purpura : a case report and literature review.2003

    • Author(s)
      Hamasaki K, Mimura T, Kanda H, Kubo K, Setoguchi K, Satoh T, Misaki Y, Yamamoto K.
    • Journal Title

      Clin Rheumatol. 22(4-5)

      Pages: 355-358

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Reconstitution of CD8+ T cells by retroviral transfer of the TCR alphabeta-chain genes isolated from a clonally expanded P815-infiltrating lymphocyte.2003

    • Author(s)
      Tahara H, Fujio K, Araki Y, Setoguchi K, Misaki Y, Kitamura T, Yamamoto K.
    • Journal Title

      J Immunol. 171(4)

      Pages: 2154-2160

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Evaluation of functional disability using the health assessment questionnaire in Japanese patients with systemic sclerosis.2003

    • Author(s)
      Kuwana M, Sato S, Kikuchi K, Kawaguchi Y, Fujisaku A, Misaki Y, Hatamochi A, Kondo H, Takehara K.
    • Journal Title

      J Rheumatol. 30(6)

      Pages: 1253-1258

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Setoguchi K, Misaki Y, Kawahata K, et al.: "Chondromodulin-I, a vantilage-derived angiogenesis inhibitory factor, suppresses T cell response."Arthritis & Rheumatism. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Kobari Y, Misaki Y, Setoguchi K, et al.: "T cell accumulating in the inflamed joints of a spontaneous murine model of rheumatoid arthritis become restricted to common clonotype."International Immunology. 16(1). 131-138 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tabara H, Fujo K, Misaki Y, et al.: "Reconstituted of CD8 T Cells by retroviral transfer of the TCR alphabeta-chain genes isolated from a clonally expanded."Journal of Immunology. 171(4). 2154-2160 (2003)

    • Related Report
      2003 Annual Research Report

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

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