2004 Fiscal Year Final Research Report Summary
Development of a novel therapy for the treatment of chronic colitis based on the manipulation of mucosal immune response and the clarification of tissue specific system for epithelial regeneration.
| Project/Area Number |
15390229
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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 |
Gastroenterology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
WATANABE Mamoru Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Professor, 大学院・医歯学総合研究科, 教授 (10175127)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Tetsuya Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Instructor, 大学院・医歯学総合研究科, 助手 (70265809)
AZUMA Miyuki Tokyo Medical and Dental University, Department of Molecular Immunology, Professor, 大学院・医歯学総合研究科, 教授 (90255654)
ISHIKAWA Hiromichi Keio University, School of Medicine, Microbiology and Immunology, Professor, 医学部, 教授 (20051667)
KIYONO Hiroshi The University of Tokyo, The Institute of Medical Science, Professor, 医科学研究所, 教授 (10271032)
HANDA Hiroshi Tokyo Institute of Technology, Frontier Collaborative Research Center, Professor, 大学院・生命理工学フロンティア創造共同研究センター, 教授 (80107432)
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| Project Period (FY) |
2003 – 2004
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| Keywords | mucosal immunity / IL-7 / intestinal epithelial cell / cell differentiation / chronic colitis / transcriptional factor / bone marrow cell / regenerative medicine |
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| Research Abstract |
The present study was a sprouting study following our original findings of the IL-7/IL-7 receptor system within the intesine, and provided successful findings in the area of human mucosal immunology, such as the origin of intestinal epithelial cells, the mechanism of the growth and differentiation of intestinal lymphocytes or interactions between mucosal epithelial cells and lymphocytes, all of which were aimed to establish a novel therapy for chronic colitis based on our original concept integrating the manipulation of the local immune response and induction of tissue regeneration within the human intestine. During the corresponding two years of study, we have accomplished series of studies following our initial study plan, and have achieved following results. 1)We have showed that IL-7 production from intestinal epithelial cells is closely involved in the induction of colitis, and that lymphocytes expressing high levels of IL-7 receptor may be a novel target for the treatment of chro
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nic colitis (Am J Physiol, 2005, in press). 2)We have demonstrated the novel mechanism of IL-7 production by intestinal epithelial cells depending on transcription factors IRF-1 and IRF-2, and provided evidences that manipulation of IRF-dependent transcription may be effective for the treatment of chronic colitis (Mol Cell Biol 2004). 3)We also demonstrated that IRE-1 is expressed specifically in goblet cells of the intestine, and functions as a master switch for the concerted expression of immuno-proteasome subunits, which provides further evidences that goblet cells play specific roles in the regulation of immune response within the intestine (FEBS Lett, 2005, in press). 4)Finally, we demonstrated that bone marrow derived cells rescue the regeneration of intestinal epithelial cells by providing increased number of bone marrow-derived secretory-type epithelial cells (including goblet cells), which in combination with 3), provided scientific basis for the establishment of lineage-specific, inductive regeneration therapy (Gastroenterology, 2005, in press). Consequently, the previous four major projects conducted in the present study have provided various meaningful results which would lead to the establishment of both novel strategy for the repression of chronic colitis or food allergy and regenerative therapy of the intestine, by integrating the regulation of intestinal mucosal immune response and the induction of tissue regeneration. Less
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Research Products
(12 results)
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[Journal Article] Increase of bone marrow-derived secretary lineage epithelial cells during regeneration in the human intestine.2005
Author(s)
Matsumoto T, Okamoto R, Yajima T, Mori T, Okamoto S, Ikeda Y, Mukai M, Yamazaki M, Nakamura T, Kanai T, Hibi T, Inazawa J, Watanabe M.
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Journal Title
Gastroenterology. (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Interferon regulatory factor 1 (IRE-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells.2004
Author(s)
Oshima S, Nakamura T, Namiki S, Okada E, Tsuchiya K, Okamoto R, Yamazaki M, Yokota T, Aida M, Yamaguchi Y, Kanai T, Handa H, Watanabe M.
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Journal Title
Mol Cell Biol. 24
Pages: 6298-6310
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hyperexpression of inducible costimulator and its contribution on lamina propria T cells in inflammatory bowel disease.2004
Author(s)
Sato T, Kanai T, Watanabe M, Sakuraba A, Okamoto S, Nakai T, Okazawa A, Inoue N, Totsuka T, Yamazaki M, Kroczek RA, Fukushima T, Ishii H, Hibi T.
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Journal Title
Gastroenterology. 126
Pages: 829-839
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Ectopic CD40 ligand expression on B cells triggers intestinal inflammation.2004
Author(s)
Kawamura T, Kanai T, Dohi T, Uraushihara K, Totsuka T, Iiyama R, Taneda C, Yamazaki M, Nakamura T, Higuchi T, Aiba Y, Tsubata T, Watanabe M.
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Journal Title
J Immunol. 172
Pages: 6388-6397
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] CD4+CD25^<bright> T cells in human intestinal lamina propria as regulatory cells.2004
Author(s)
Makita S, Kanai T, Oshima S, Uraushihara K, Totsuka T, Iiyama R, Sawada T, Nakamura T, Koganei K, Fukushima T, Watanabe M.
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Journal Title
J Immunol. 173
Pages: 3119-3130
Description
「研究成果報告書概要(欧文)」より
