| Project/Area Number |
13306010
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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 |
食品科学・栄養科学
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
KAMINOGAWA Shuichi THE UNIVERSITY OF TOKYO, The University of Tokyo GRADUATE SCHOOL OF AGRICULTURAL AND LIFE SCIENCES, PROFESSOR (50011945)
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| Co-Investigator(Kenkyū-buntansha) |
HACHIMURA Satoshi 東京大学, GRADUATE SCHOOL OF AGRICULTURAL AND LIFE SCIENCES, ASSOCIATE PROFESSOR (40238019)
TOTSUKA Mamoru 東京大学, GRADUATE SCHOOL OF AGRICULTURAL AND LIFE SCIENCES Visiting ASSOCIATE PROFESSOR, Visting ASSOCIATE PROFESSOR (70227601)
YAMADA Kiyoshi 東京大学, GRADUATE SCHOOL OF AGRICULTURAL AND LIFE SCIENCES, Visting Research Assistant (30313076)
ISE Wataru 東京大学, GRADUATE SCHOOL OF AGRICULTURAL AND LIFE SCIENCES, Research Assistant (70323483)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥47,190,000 (Direct Cost: ¥36,300,000、Indirect Cost: ¥10,890,000)
Fiscal Year 2002: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2001: ¥30,420,000 (Direct Cost: ¥23,400,000、Indirect Cost: ¥7,020,000)
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| Keywords | food allergy / intestinal immune system / T cell / intraepithelial lymphocytes(IEL) / oral tolerance / IgE / intestinal epithelial cells / raffinose / DNAマイクロアレー / プロテオーム解析 / 小腸上皮細胞(IEC) |
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| Research Abstract |
1. Molecular biological analysis of characteristics of gut immunity (1) DNA microarray analysis identified genes expressed more abundantly in IEL than in spleen T cells. (2) We also elucidated the change in the gene expression pattern in EEL when ovalbumin (OVA)-specific T-cell receptor transgenic (TCR-Tg) mice were fed an egg-white diet. (3) The method for the primary culture of murine fetal intestinal epithelial cells was established and its capability for antigen presentation was shown.
2. Analysis of mechanisms of oral tolerance induction (1) We showed that oral tolerance was induced in PP-deficient mice. (2) Intracellular proteins specifically expressed in orally tolerized CD4 T cells were determined by two-dimensional electrophoresis and mass spectrometric analysis. The results demonstrated that Caspase 3 was upregulated in orally tolerant CD4 T cells. (3) Genes expressed specifically in orally tolerized CD4 T cells were cloned using subtractive hybridization.
3. Analysis of food allergy model, and suppression of food allergic reactions by food-derived immune functional molecules. (1) Feeding OVA diet to OVA-specific TCR-Tg mice resulted not only in induction of a serum IgE response, but also in inflammation in the small intestine. OVA-specific antibodies elicited by feeding OVA recognized mainly the tertiary structure of OVA. (2) OVA-specific IgE production and the decrease in body weight induced in this food-allergy model were shown to be suppressed by administering a TCR-antagonistic analog of the antigenic OVA peptide. (3) Feeding raffinose, which is known to modulate intestinal microflora, suppressed the IgE response in this food allergy model. (4) We also showed that the cytokine secretion pattern of naive CD4+ T cells were altered depending on the dose of OVA-derived peptide as an antigenic peptide.
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