| Project/Area Number |
13GS0015
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| Research Category |
Grant-in-Aid for Creative Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Institution | Keio University |
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Principal Investigator |
ISHIKAWA Hiromichi Keio University, School of Medicine, Professor (20051667)
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| Co-Investigator(Kenkyū-buntansha) |
SUEMATSU Makoto Keio University, School of Medicine, Professor (00206385)
KOYASU Shigeo Keio University, School of Medicine, Professor (90153684)
OHTEKI Toshiaki Akita University, School of Medicine, Professor (50233200)
WATANABE Mamoru Tokyo Medical and Dental University, Graduate School, Department of Gastroenterology and Hepatology, Professor (10175127)
HACHIMURA Satoshi University of Tokyo, Graduate School of Agricultural and Life Sciences, Department of Applied Biological Chemistry, Associate Professor (40238019)
日比 紀文 慶應義塾大学, 医学部, 教授 (50129623)
合田 宣人 慶應義塾大学, 医学部, 講師 (00245549)
阿部 啓子 東京大学, 大学院・農業生命科学研究科, 教授 (10151094)
田之倉 優 東京大学, 大学院・農学生命科学研究科, 教授 (60136786)
清水 誠 東京大学, 大学院・農学生命科学研究科, 教授 (30114507)
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| Project Period (FY) |
2001 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥395,330,000 (Direct Cost: ¥326,930,000、Indirect Cost: ¥68,400,000)
Fiscal Year 2005: ¥98,800,000 (Direct Cost: ¥76,000,000、Indirect Cost: ¥22,800,000)
Fiscal Year 2004: ¥98,800,000 (Direct Cost: ¥76,000,000、Indirect Cost: ¥22,800,000)
Fiscal Year 2003: ¥98,800,000 (Direct Cost: ¥76,000,000、Indirect Cost: ¥22,800,000)
Fiscal Year 2002: ¥98,930,000 (Direct Cost: ¥98,930,000)
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| Keywords | dietary substances / immunology / intestinal flora / γδ T cells / intestinal T cells / secretory IgA antibody / cryptopatch / isolated lymphoid follicles / 経口免疫寛容 / 炎症性腸疾患 / 腸管上皮細胞間T細胞 / 生体分子 / トランスレーショナルリサーチ / 腸管孤立リンパ小節 / 分泌型lgA抗体 / 腸内常在フローラ / 腸管上皮細胞 / 樹状細胞 / インターロイキン15 / Heme oxygenase / 一酸化炭素 |
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| Research Abstract |
We started the above research project in 2001, and since 2001, distinctive features of functional crosstalk between intestinal flora, intestinal epithelial cells (IEC) and local as well as entire immune responses have been accumulated. Now, it is evident that intestinal flora and dietary substances that determine the composition of intestinal flora are important to the establishment of distinctive feature of intestinal immune response. Furthermore, it is speculated that the alteration of intestinal flora by modern dietary substances are involved in the pathogenesis of ulcerative colitis and Crohn's disease.
With regard to the summary of the research project, it should be pointed out that we clarified several distinctive aspects of intestinal immune response. First, acute graft-versus-host disease (aGVHD) is initiated by immunologically competent cytotoxic T cells (CTL) that express anti-host specificities. We have corroborated for the first time that gut Peyer's patches (PP) are required to activate anti-host CTL response in a well characterized murine aGVHD model. Second, we have verified that all lymph nodes including mesenteric lymph nodes, PP and isolated lymphoid follicles are not an absolute requirement for the histogenesis of recently discovered gut cryptopatches (CP) and development of γδ-IEL in the athymic nu/nu mice. These results indicate that gut CP might be the anatomical sites to generate progenitor γδ-IEL under this extreme lymphoid depletion. Third, it has been demonstrated that interleukin 15-dependent crosstalk between conventional and plasmacytoid dendrite cells is essential for CpG-induced immune activation. Taking all of these new findings together, we have accumulated new important evidence that is essential for the investigation of immuno-regulatory competency of dietary substances and its application for our own beneficial ends.
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