| Project/Area Number |
17390293
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Laboratory for Signal Network, Research Center for Allergy and Immunology (RCAI), RIKEN Yokohama Institute |
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Principal Investigator |
KUBO Masato RIKEN Yokohama Institute, Laboratory for Signal Network, Center for Allergy and Immunology (RCAI), シグナル・ネットワーク研究チーム, チームリーダー (40277281)
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| Co-Investigator(Kenkyū-buntansha) |
八木 良二 独立行政法人理化学研究所, シグナル・ネットワーク研究チーム, 研究員 (20392152)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2006: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2005: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | IL-4 / Chromatin / Notch / Memory T cell / Transcriptional factor / IL-2 |
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| Research Abstract |
From our previous study, the expression of IL-4 gene is found to be epigenetically regulated in CD4^+ T cells. However, these gene regulation mechanisms are virtually unclear. Therefore, we investigated the role of an evolutionarily conserved 〜200bp non-coding sequence in the intergenic region between IL-4 and KIF3 genes using GFP reporter transgenic (Tg) mice. Notch signals have been shown to affect the cellular differentiation of tissue throughout the life of multicellular organisms. RBP-Jκ is a downstream common transcriptional mediator in Notch signaling. The T cell specific deficiency of RBP-J□ resulted in selective loss of Th2 development. Distal 3' enhancer in Il4 locus that correlates with the conserved regions called, Conserved non-coding sequences (CNS)-2, contained multiple possible binding sites for RBP-Jκ. Using a transgenic GFP reporter system, we showed that binding of RBP-Jκ to the CNS-2 enhancer regulated initial IL-4 production from NKT cells and a subset of CD44^<hi> memory phenotype (MP) CD4 T cells. The Rbp-j deficient T cells exhibited marked reduction of both CNS-2 enhancer activity and initial IL-4 from NKT and MP CD4 T cells. Depletion of CNS-2 active CD4 T cells markedly decreased Th2 differentiation from naive CD4 T cells. These results indicate the functional importance of Notch signal and MP CD4 T cells in facilitating Th2 differentiation of naive CD4 T cells during initial stage of antigen induced allergic responses.
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