| Project/Area Number |
12670441
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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 |
内科学一般
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| Research Institution | Research Institute Biological Sciences, Tokyo Universjty of Science |
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Principal Investigator |
MASATO Kubo Research Institute Biological Sciences, Tokyo Universjty of Science,Associate,professor, 生命科学研究所, 助教授 (40277281)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | genome / T cell differentiation / Th1 / Th2 / IL-4 |
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| Research Abstract |
The differentiation of naive, uncommitted Th cell precursors into Thi or Th2 cells is cell-cycle dependent process that is initiated by antigen and cytokine stimulation. Both T cell receptor (TCR) cross-linking and Interleukin (IL)-4 is known to be required for onset of Th2 commitment. However, how these two signals synergistically regulate Th2 differentiation poorly understand. We established the transgenic mice expressing human lL-4 receptor (hlL-4R Tg) to distinguish IL-4-dependent signal from TCR signal during induction of helper T cell differentiation. The addition of hlL-4 at initial ICR stimulation completely substituted the function of endogenous lL-4 required for Th2 generation. Timedependent kinetics analysis revealed that the presence of IL-4 within 36 hr after TCR activation that a large number of T cells remained at first cell cycle, was a critical for the onset of Th2 commitment and chromatin remodeling on IL-4 gene locus. In contrast, the addition of lL-4 after proceeding cell division did not result in efficient Th2 differentiation. In TCR activated T cells from hlL-4R Tg, GATA-3 expression was depend on the addition of hlL-4 even at the time points when no Th2 cells was generated. Ectopic expression of GATA-3 showed that timing and expression level was critical for determination of lineage commitment towards Th2 cells. These results indicate that a direction of I cell commitment is almost determined at first cell division, and IL-4 mediated GATA-3 expression at this stage may control efficient Th2 differentiation.
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