2008 Fiscal Year Final Research Report
Circulating colitogenic CD4+ memory T cells between bone marrow and intestine may be targets for the treatment of inflammatory bowel diseases
Project/Area Number |
19390197
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Keio University (2008) Tokyo Medical and Dental University (2007) |
Principal Investigator |
KANAI Takanori Keio University, 医学部, 准教授 (40245478)
|
Co-Investigator(Kenkyū-buntansha) |
WATANABE Manabu 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (10175127)
TOTSUKA Teruji 東京医科歯科大学, 医学部・附属病院, 助教 (70447465)
NAGAISHI Takashi 東京医科歯科大学, 医歯(薬)学総合研究科, メディカルフェロー (60447464)
|
Project Period (FY) |
2007 – 2008
|
Keywords | 炎症性腸疾患 / 腸炎責任CD4 T 細胞 / 免疫記憶T 細胞 / IL-7 / 慢性大腸炎モデル |
Research Abstract |
マウス大腸炎モデルにおいて腸炎責任CD4T細胞は腸炎完成後恒常的に全身循環し、循環遮断は腸炎発症を抑制することを明らかとした。腸炎責任CD4T細胞はIL-7産生骨髄にも存在し、腸管IL-7欠損状態においても骨髄IL-7によって維持されることを並体結合実験で証明した。さらに、腸炎責任CD4T細胞はTLR分子を発現し、MyD88分子を介し病態恒常性に寄与することを明らかとした。また、無菌マウスにおいても腸炎発症を認めることはないものの腸炎責任CD4 T細胞は恒常的生体内で長期維持されることを証明した。
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[Journal Article] RANK-RANKL signaling pathway is critically involved in the function of CD4+CD25+ regulatory T cells in chronic colitis2009
Author(s)
Totsuka T, Kanai T, Nemoto Y, Tomita T, Okamoto R, Tsuchiya K, Nakamura T, Sakamoto N, Akiba H, Okumura K, Yagita H, Watanabe M.
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Journal Title
J Immunol 182
Pages: 6079-6087
Peer Reviewed
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[Journal Article] Signaling pathway via TNF-alpha/NF-kappaB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis2009
Author(s)
Onizawa M, Nagaishi T, Kanai T, Nagano K, Oshima S, Nemoto Y, Yoshioka A, Totsuka T, Okamoto R, Nakamura T, Sakamoto N, Tsuchiya K, Aoki K, Ohya K, Yagita H, Watanabe M.
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Journal Title
Am J Physiol Gastrointest Liver Physiol 296
Pages: 850-859
Peer Reviewed
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[Journal Article] Colitogenic CD4+ effector-memory T cells actively recirculate in chronic colitic mice2008
Author(s)
Tomita T, Kanai T, Nemoto Y, Fujii T, Nozaki K, Okamoto R, Tsuchiya K, Nakamura T, Sakamoto N, Totsuka T, Watanabe M.
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Journal Title
Inflamm Bowel Dis. 14
Pages: 1630-1640
Peer Reviewed
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[Journal Article] Negative feedback regulation of colitogenic CD4+ T cells by increased granulopoiesis2008
Author(s)
Nemoto Y, Kanai T, Tohda S, Totsuka T, Okamoto R, Tsuchiya K, Nakamura T, Sakamoto N, Fukuda T, Miura O, Yagita H, Watanabe M
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Journal Title
Inflamm Bowel Dis. 14
Pages: 1491-1503
Peer Reviewed
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[Journal Article] Development of plaque assays for hepatitis C virus-JFH1 strain and isolation of mutants with enhanced cytopathogenicity and replication capacity2008
Author(s)
Sekine-Osajima Y, Sakamoto N, Mishima K, Nakagawa M, Itsui Y, Tasaka M, Nishimura-Sakurai Y, Chen CH, Kanai T, Tsuchiya K, Wakita T, Enomoto N, Watanabe M.
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Journal Title
Virology 371
Pages: 71-85
Peer Reviewed
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[Journal Article] Blockade of NKG2D signaling prevents the development of murine CD4+ T cell-mediated colitis2008
Author(s)
Ito Y, Kanai T, Totsuka T, Okamoto R, Tsuchiya K, Nemoto Y, Yoshioka A, Tomita T, Nagaishi T, Sakamoto N, Sakanishi T, Okumura K, Yagita H, Watanabe M.
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Journal Title
Am J Physiol Gastrointest Liver Physiol 294
Pages: 199-207
Peer Reviewed
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