Novel therapeutic strategy for ulcerative colitis by targeting NKT cells
| Project/Area Number |
21590806
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 |
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| Co-Investigator(Kenkyū-buntansha) |
NAGAISHI takashi 東京医科歯科大学, 医学部附属病院, 助教 (60447464)
ARAKI Akihiro 東京医科歯科大学, 医学部附属病院, 講師 (80361690)
OKAMOTO Ryuichi 東京医科歯科大学, 大学院・医歯学総合研究科, 寄附講座教員 (50451935)
WATANABE Mamoru 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (10175127)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 炎症性腸疾患 / 潰瘍性大腸炎 / 粘膜免疫 / 新規治療法 / NKT細胞 |
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| Research Abstract |
Background and Aims : Inflammatory Bowel Disease(IBD) is characterized by unrestrained lymphocyte activation that results in the production of a variety of pro-inflammatory cytokines and other mediators. Understanding the mechanisms of lymphocyte regulation is therefore of significant importance to dysregulated mucosal inflammation in IBD. It has been reported that natural killer T(NKT) cells express pro-inflammatory cytokine such as IL-13 in the colonic tissues of patients with ulcerative colitis(UC). CD1d is a major histocompatibility complex class I-related molecule that functions in the presentation of glycolipid antigens to invariant(i) NKT cells. The mechanism(s) by which CD1d acquires glycolipid antigens for presentation to such cells is however unknown. Microsomal triglyceride transfer protein(MTP), encoded by the Mttp gene, is an endoplasmic reticulum resident protein expressed by intestinal epithelial cells(IEC) which is essential for the lipidation of apolipoprotein-B. The aim of this study was to demonstrate whether MTP also regulates CD1d-restricted antigen presentation by these cells. Materials and Methods : Protein lysates of intestinal epithelia from wild type(WT) C57BL/6(B6) mice were immunoprecipitated with an anti-CD1d monoclonal antibody(mAb) and probed by Western blotting with an anti-MTP mAb to investigate CD1d and MTP interactions. Fresh cryosections of colons from the intestinal epithelia-specific MTP deficient mice or the murine IEC line, MODE-K, transfected with siRNA oligomers to silence Mttp gene expression were stained with an anti-CD1d mAb to assess the distribution of CD1d expression. WT B6 or the MTP deficient mice were subjected to oxazolone-induced colitis and examined for clinical and pathological changes. Results : A direct biochemical association was observed between CD1d and MTP in intestinal epithelia. Confocal
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Report
(4 results)
Research Products
(72 results)
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[Journal Article] Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+stem cell2012
Author(s)
Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X, Ichinose S, Nagaishi T, Okamoto R, Tsuchiya K, Clevers H, and Watanabe M
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Journal Title
Nature Medicine
Volume: 18
Issue: 4
Pages: 618-623
DOI
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Peer Reviewed
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[Journal Article] MR enterocolonography is useful for simultaneous evaluation of small and large intestinal lesions in Crohn's disease.2010
Author(s)
Hyun SB, Kitazume Y, Nagahori M, Akira T, Fujii T, Tsuchiya K, Suzuki S, Okada E, Araki A, Naganuma M, Watanabe M
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Journal Title
Inflam Bowel Dis
Volume: in press
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Peer Reviewed
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[Journal Article]2009
Author(s)
長堀正和、渡辺守
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Journal Title
【炎症性腸疾患 診断と治療の進歩】潰瘍性大腸炎の管理・治療 潰瘍性大腸炎の内科治療(解説/特集)日本内科学会雑誌 98巻(日本内科学会)
Pages: 54-60
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