| Project/Area Number |
14570282
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Kumamoto University |
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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)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| 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)
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| Keywords | glucocorticoid / 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 |
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| 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.
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