2004 Fiscal Year Final Research Report Summary
Corss-talk of signals between immunoreceptors and cytokine receptors for development of allergy
| 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)
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| Project Period (FY) |
2002 – 2004
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| Keywords | allergy / cytokine / signal transduction / IgE receptor / mast cell / natural killer cell / natural killer T cell / tumor |
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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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[Journal Article] Transcriptional regulation of SLP-76 family hematopoietic cell adaptor MIST/Clnk by STAT5.2004
Author(s)
Sasanuma, H., Tatsuno, A., Tsuji, K., Hidano, S., Kitamura, T., Kuno, M., Kitamura, D., Goitsuka, R.
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Journal Title
Biochem.Biophys.Res.Comm. 321
Pages: 145-153
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] BASH-deficient mice : limited primary repertoire and antibody formation, but sufficient affinity maturation and memory B cell generation, in anti-NP response.2004
Author(s)
Yamamoto, M, Nojima, T, Hayashi, K, Goitsuka, R, Furukawa, K, Azuma, T, Kitamura, D.
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Journal Title
Int.Immunol. 16
Pages: 1161-1171
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Targeting of MIST to Src-family kinases via SKAP55-SLAP-130 adaptor complex in mast cells.2003
Author(s)
Fujii, Y., Wakahara, S., Nakao, T., Hara, T., Ohtake, H., Komurasaki, T., Kitamura, K., Tatsuno, A., Fujiwara, N., Hozumi, N., Ra, C., Kitamura, D., Goitsuka, R.
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Journal Title
FEBS Letters 540
Pages: 111-116
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Distinct signaling requirements for Dμ selection, IgH allelic exclusion, pre-B cell transition, and tumor suppression in B cell progenitors.2003
Author(s)
Hayashi, K., Yamamoto, M., Nojima, T., Goitsuka, R., Kitamura, K.
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Journal Title
Immunity 18
Pages: 825-836
Description
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