| Project/Area Number |
14206034
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
GOITSUKA Ryo Tokyo University of Science, Research Institute for Biological Sciences, Associate Professor, 生命科学研究所, 助教授 (50301552)
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| Co-Investigator(Kenkyū-buntansha) |
KITAMURA Daisuke Tokyo University of Science, Institute for Biological Sciences, Professor, 生命科学研究所, 教授 (70204914)
香山 雅子 東京理科大学, 生命科学研究所, 助手 (80318229)
久保 允人 東京理科大学, 生命科学研究所, 助教授 (40277281)
林 克彦 東京理科大学, 生命科学研究所, 助手 (20287486)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥42,510,000 (Direct Cost: ¥32,700,000、Indirect Cost: ¥9,810,000)
Fiscal Year 2004: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Fiscal Year 2003: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2002: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
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| Keywords | allergy / cytokine / signal transduction / IgE receptor / mast cell / natural killer cell / natural killer T cell / tumor / メモリー細胞 / NK細胞 / NKT細胞 |
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| Research Abstract |
Various immune cells including mast cells and NKT cells are involved in allergic diseases. These cells express immunoreceptors that react with immunoglobulin E(IgE) or various antigens, and are activated by signals delivered by the interaction of receptors with their respective ligands. In adddition, cytokines produced by these cells deteriorate allergic inflammation. MIST is a member of SLP-76 family adaptor proteins that are involved in immunoreceptor signal transduction, and is expressed in a variety of cytokine-dependent hematopoietic cell lines of myeloid and lymphoid origin. We have demonstrated in the present study that STAT5 is involved in cytokine-mediated up-regulation of MIST gene expression in mast cells by analyzing transcription regulatory elements of the MIST gene. Furthermore, we have revealed that MIST functions as a positive regulator for high-affinity IgE receptor-mediated mast cell degranulation and cytokine production by using MIST-deficient mice. TCR-mediated IFN-γ and IL-4 production by NKT cells was also positively regulated by MIST. In contrast, MIST appears to act as a negative regulator for NK cell receptor-mediated IFN-γ production. This functional conversion of MIST was regulated by the interaction of MIST with Fgr, an Src family kinase expressed in NK cells but not in NKT cells, indicating MIST as an important molecular switch to control diverse responses in different cell populations. Taken together, MIST serves as a link between immunoreceptor- and cytokine-signaling, and can enhance immunoreceptor-mediated activation of immune cells at the site of allergic reactions where abundant cytokines are accumulated. Thus, suppression of MIST expression and/or function could be a potential target for anti-allergic therapy, since MIST deficiency lower the threshold for receptor-mediated activation of mast cells and NKT cells.
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