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Regulatory mechanism of glucocorticoid for B lymphocyte activation and development

Research Project

Project/Area Number 14570282
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKumamoto University

Principal Investigator

IGARASHI Hideya  School of Medicine Kumamoto University, Department of Immunology, Graduate School of Medical Sciences, Instructor, 大学院・医学薬学研究部, 助手 (40291538)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsglucocorticoid / B cell activation / B cell development / グルココルチコイド / GR / G5PR / フォスファターゼ / PP2A / PP5 / GANP
Research Abstract

Patterns of lymphoid progenitor deficiency in some patient marrow specimens suggested these cells might be affected by anti-inflammatory therapy. Supportive evidence for this possibility was obtained with culture and chimeric animal experiments, where human lymphoid progenitors were preferentially depressed by exposure to glucocorticoids. Studies conducted with dexamethasone treated mice revealed selective depletion of cycling B lineage precursors. In contrast, mature, non-dividing CD45R^<Hi> CD19^<Hi> lymphocytes, myeloid progenitors and stem cells with the potential for lymphocyte generation on transplantation were spared. Lin^-IL-7R^+ Flk-2^+ pro-lymphocytes also declined, but not as rapidly as the TdT^+ cells within an early Lin^-c-kit^<Hi> Sca-1^<Hi> fraction of bone marrow. Hormone sensitive cells with additional properties of early lymphocyte progenitors were identified within the same Lin^-c-kit^<Hi> Sca-1^<Hi> subset using human m transgenic mice and RAG1/GFP knock-in animals. Furthermore, cells with a recent history of RAG1 expression were more glucocorticoid sensitive than mature lymphocytes in marrow and spleen. Lymphocyte progenitors in mice bearing a human bcl-2 transgene were protected from dexamethasone treatment. However, isolated progenitors from either wild type or bcl-2 transgenic mice were directly sensitive to the hormone in stromal cell-free cultures. B lineage lymphocyte precursors were found to be abnormally elevated in bone marrow of adrenalectomized or RU486 treated mice. This suggests that glucocorticoids may normally contribute to steady-state regulation of lymphopoiesis. These findings are informative about means for controlling lymphocyte production in central lymphoid organs and suggest experimental approaches for determining the sequence of early differentiation events.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Takafumi Yokota, et al.: "Adiponectin, a fat cell product, influences the earliest lymphocyte precursors in bone marrow cultures by activation of the cyclooxygenase-prostaglandin pathway in stromal cells"J.Immunol.. 171. 5091-5099 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takafumi Yokota, et al.: "Unique properties of fetal lymphoid progenitors identified according to RAG1 gene expression."Immunity. 19. 365-375 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jun Hirose, et al.: "A developing picture of lymphopoiesis in bone marrow."Immunol.Rev.. 189. 28-40 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideya Igarashi, et al.: "Transcription from the RAG1 locus marks the earliest lymphocyte precursors in bone marrow."Immunity. 17. 117-130 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Paul W.Kincade, et al.: "Lymphoid lineage cells in adult murine bone marrow diverge from those of other blood cells at an early, hormone sensitive stage."Semin Immunol.. 14. 385-394 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takafumi Yokota, C.S.Reddy Meka, Taku Kouro, K.L.Medina, Hideya Igarashi, Masahiko Takahashi, Kenji Oritani, Tohru Funahashi, Yashiaki Tomiyama, Yuji Matsuzawa, Paul W.Kincade: "Adiponectin, a fat cell product, influences the earliest lymphocyte precursors in bone marrow cultures by activation of the cyclooxygenase-prostaglandin pathway in stromal cells."J.Immunol.. 171. 5091-5099 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takafumi Yokota, Taku Kouro, Jun Hirose, Hideya Igarashi, Karla P.Garrett, Sophia C.Gregory, Nobuo Sakaguchi, John J.T.Owen, Paul W.: "Kincade Unique properties of fetal lymphoid progenitors identified according to RAG1 gene expression."Immunity. 18. 365-375 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Jun Hirose, Taku Kouro, Hideya Igarashi, Takafumi Yokota, Nobuo Sakaguchi, Paul W.Kincade: "A developing picture of lymphopoiesis in bone marrow"Immunol.Rev.. 189. 28-40 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideya Igarashi, Sophia C.Gregory, Takafumi Yokota, Nobuo Sakaguchi, Paul W.Kincade: "Transcription from the RAG1 locus marks the earliest lymphocyte precursors in bone marrow."Immunity. 17. 117-130 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Paul W.Kincade, Hideya Igarashi, Kay L.Medina, Taku Kouro, Takafumi Yokota, Maria Isabel D.Rossi, John J.T.Owen, Karla P.Garrett, Xiao-Hong Sun, Nobuo Sakaguchi: "Lymphoid lineage cells in adult murine bone marrow diverge from those of other blood cells at an early, hormone sensitive stage."Semin Immunol.. 14. 385-394 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Paul W.Kincade, John J.T.Owen, Hideya Igarashi, Taku Kouro, Takafumi Yokota, Maria Isabel D.Rossi: "Nature or Nurture? Steady state lymphocyte formation in adults does not recapitulate ontogeny."Immunol.Rev.. 187. 116-125 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takafumi Yokota, et al.: "Adiponectin, a fat cell product, influences the earliest lymphocyte precursors in bone marrow cultures by activation of the cyclooxygenase-prostaglandin pathway in stromal cells"J.Immunol.. 171. 5091-5099 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takafumi Yokota, et al.: "Unique properties of fetal lymphoid progenitors identified according to RAG1 gene expression"Immunity. 19. 365-375 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jun Hirose, et al.: "A developing picture of lymphopoiesis in bone marrow"Immunol.Rev.. 189. 28-40 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hideya Igarashi, et al.: "Transcription from the RAG1 locus marks the earliest lymphocyte precursors in bone marrow"Immunity. 17. 117-130 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Paul W.Kincade, et al.: "Lymphoid lineage cells in adult murine bone marrow diverge from those of other blood cells at an early, hormone sensitive stage"Semin Immunol.. 14. 385-394 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Paul W.Kincade, et al.: "Nature or Nurture? Steady state lymphocyte formation in adults does not recapitulate ontogeny"Immunol.Rev.. 187. 116-125 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jun Hirose: "A developing picture of lymphopoiesis in bone marrow"Immunol Rev. 189. 28-40 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hideya Igarashi: "Transcription from the RAG1 locus marks the earliest lymphocyte precursors in bone marrow"Immunity. 17. 117-130 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Paul W.Kincade: "Lymphoid lineage cells in adult murine bone marrow diverge from those of other blood cells at an early, hormone sensitive stage"Semin Immunol.. 14. 385-394 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Paul W.Kincade: "Nature or Nurture? Steady state lymphocyte formation in adults does not recapitulate ontogeny"Immunol. Rev. 187. 116-125 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takafumi Yokota: "Paracrine regulation of fat cell formation in bone marrow cultures via adiponectin and prostaglandins"J. Clin. Invest.. 109. 1303-1310 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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