2002 Fiscal Year Final Research Report Summary
Elucidation of the mechanism for regurating mucosal immune response and application for the treatment of chronic colitis and food allergy.
| Project/Area Number |
13470116
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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) |
ISHIKAWA Hiromichi Keio University, School of Medicine, Microbiology and Immunology, Professor, 医学部, 教授 (20051667)
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)
KANAI Takanori Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Instructor, 医学部附属病院, 助手 (40245478)
KIYONO Hiroshi Research Institute for Microbial Disease Osaka University, Department of Mucosal Immunology, Professor, 微生物病研究所, 教授 (10271032)
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| Project Period (FY) |
2001 – 2002
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| Keywords | IL-7 / IL-7 receptor / mucosal jmmunity / regenerative medicine / intestinal epithelial cell / bone marrow cell / chronic cohtis / food allergy |
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| Research Abstract |
We have established a concept of intramucosal network system composed of IL-7-producing epithelial cells and IL-7R-expressing lymphoid cells, and clarified the significant roles of this network in mucosal immune regulation within the gut. In the current project, we have attempted to further elucidate the regulatory mechanisms of mucosal immune system concerning the IL-7/IL-7R network and the intestinal epithelial cell (IEC) functions. Until present, we have developed an experimental system where IL-7R-expressing cells are efficiently targeted by in vivo administration of immunotoxic anti-IL-7R antibodies that are linked to saporin. Our findings that direct immunotoxin targeting of DL-7R caused significant amelioration of chronic colitis in several model mice proposed the IL-7/IL-7R system to be a novel therapeutic target for a certain type of chronic colitis in humans. We have also investigated the physiology of BECs and have reported that bone marrow (BM)-derived cells can repopulate the epithelia of the human gastrointestinal tract. Moreover, the potentials of BM cells to transdifferentiate into lECs are shown to be important for the promotion ofregenerating process of severely damaged epithelia. Further analysis and integration of the results of our investigations would provide not only a better understanding of the mechanisms of mucosal immune regulation, but also potential therapeutic approaches directed to immune regulation and promotion of tissue repair in human diseases.
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Research Products
(10 results)
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[Publications] Inoue, N., Watanabe, M., Sato, T., Okazawa, A., Yamazaki, M., Kanai, T., Ogata, H., Iwao, Y., Ishii, H., Hibi, T.: "Restricted V_H gene usage in lamina propria B cells producing anticolon antibody from parients with ulcerative colitis"Gastroenterology. 121. 15-23 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kanai, T., Watanabe, M., Okazawa, A., Sato, T., Yamazaki, M., Okamoto, S., Ishii, H., Totsuka, T., liyama, R., Okamoto, R., Ikeda, M., Kurimoto, M., Takeda, K., Akira, S., Hibi, T.: "Macrophage-derived IL-18 mediated intestinal inflammation in the murine model of Crohn's disease"Gastroenterology. 121. 875-888 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sasazuki, T., Sawada, T., Sakon, S., Kitamura, T., Kishi, T., Okazaki, T., Katano, M., Tanaka, M., Watanabe, M., Yagita, H., Okamura, K., Nakano, H.: "Identification of a Novel Transcriptional activator, BSAC, by a Functional Cloning to Inhibit Tumor Necrosis Factorinduced Cell Death"J Biol Chem. 277. 28853-28860 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Okamoto, R., Yajima, T., Yamazaki, M., Kanai, T., Mukai, M., Okamoto, S., Ikeda, Y., Hibi, T., Inazawa, J., Watanabe, M.: "Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract"Nature Med. 8. 1011-1017 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Totsuka, T., Kanai, T., liyama, R., Uraushihara, K., Yamazakd, M., Okamoto, R., Hibi, T., Tezuka, K., Azuma, M., Akiba, H., Yagita, H., Okumura, K., Watanabe, M.: "Ameliorating Effect of Anti-Inducible CoStimulator Monoclonal Antibody in a Murine Model of Chronic Colitis"Gastroenterology. 124. 410-421 (2002)
Description
「研究成果報告書概要(欧文)」より
