Antigen processing in intestinal epithelial cells
| Project/Area Number |
16H05286
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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 |
NAGAISHI Takashi 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (60447464)
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| Co-Investigator(Kenkyū-buntansha) |
中村 哲也 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座教授 (70265809)
渡辺 守 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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| Research Collaborator |
ONIZAWA Michio
SUZUKI Masahiro
WATABE Taro
TSUGAWA Naoya
YAMADA Daiki
KOJIMA Yudai
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 炎症性腸疾患 / 粘膜免疫 / 抗原提示 |
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| Outline of Final Research Achievements |
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 such as IBD. Genome-wide association studies in the analysis of IBD have identified genetic risk foci. Several studies have especially revealed the important roles of antigen presentation-related genes in IBD, including the major histocompatibility complex class I and II. In this regards, we have observed that the expressions of these molecules in several cell types such as hematopoietic cells and epithelial cells were modulated by the up-regulated pro-inflammatory cytokines in vivo. Defining the mechanisms of antigen presentation will lead to a significant understanding of the manner in which manipulation of this function may provide insights into novel therapeutic methods for the treatment of IBD.
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| Academic Significance and Societal Importance of the Research Achievements |
腸管の免疫調節機構が未だ不明確であることは、炎症性腸疾患(IBD)治療法開発を困難にしている。本研究の特徴は腸管免疫調節機構に関する研究を展開してきた申請者らが、正常腸上皮細胞の初代培養技術を応用したことで、IBDの病態理解に留まらず、これまで実現し得なかった「生理的粘膜免疫応答」の機能解析に向けた技術基盤樹立という免疫学的インパクト、さらにはIBDにおける腸管粘膜傷害に対するその特異的な免疫調節異常を標的とした新規細胞治療、分子治療開発へ向けた理論、技術基盤の創出に発展するものと期待できる。
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Report
(4 results)
Research Products
(59 results)
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[Journal Article] Indolent T cell lymphoproliferative disorder with villous atrophy in small intestinediagnosed by single-balloon enteroscopy.2019
Author(s)
Takashi Nagaishi, Daiki Yamada, Kohei Suzuki, Ryosuke Fukuyo, Eiko Saito, Masayoshi Fukuda, Taro Watabe, Naoya Tsugawa, Kengo Takeuchi, Kouhei Yamamoto, Ayako Arai, Kazuo Ohtsuka, Mamoru Watanabe
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Journal Title
Clin J Gastroenterol.
Volume: in press
Pages: 434-440
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Novel polyubiquitin imaging system, PolyUb-FC, reveals that K33-linked polyubiquitin is recruited by SQSTM1/p62.2018
Author(s)
Yoichi Nibe, Shigeru Oshima, Masanori Kobayashi, Chiaki Maeyashiki, Yu Matsuzawa, Kana Otsubo, Hiroki Matsuda, Emi Aonuma, Yasuhiro Nemoto, Takashi Nagaishi, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Shinichiro Nakada, Mamoru Watanabe
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Journal Title
Autophagy
Volume: 22
Pages: 347-358
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] B cell activation in the cecal patches during the development of an experimental colitis model2018
Author(s)
Taro Watabe, Takashi Nagaishi, Naoya Tsugawa, Yudai Kojima, Nisha Jose, Akinori Hosoya, Michio Onizawa, Yasuhiro Nemoto, Shigeru Oshima, Tetsuya Nakamura, Hajime Karasuyama, Takahiro Adachi, Mamoru Watanabe
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Journal Title
Biochem Biophys res Commun.
Volume: 496
Pages: 367-373
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] HADHA, the alpha subunit of the mitochondrial trifunctional protein, is involved in long-chain fatty acid-induced autophagy in intestinal epithelial cells.2017
Author(s)
Maeyashiki C, Oshima S, Otsubo K, Kobayashi M, Nibe Y, Matsuzawa Y, Onizawa M, Nemoto Y, Nagaishi T, Okamoto R, Tsuchiya K, Nakamura T, Watanabe M
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Journal Title
Biochem. Biophys. Res. Commun
Volume: 484
Pages: 636-641
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] The ubiquitin hybrid gene UBA52 regulates ubiquitination of ribosome and sustains embryonic development.2016
Author(s)
Kobayashi M, Oshima S, Maeyashiki C, Nibe Y, Otsubo K, Matsuzawa Y, Memoto Y, Nagaishi T, Okamoto R, Tsuchiya K, Nakamura T, Watanabe M
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Journal Title
Sci Rep
Volume: 6
Pages: 36780-36780
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] CEACAM1 regulation of BCR signaling in the activated B cells.2016
Author(s)
Akinori Hosoya, Takashi Nagaishi, Arisa Tokai, Taro Watabe, Nisha Jose, Yudai Kojima, Motomi Yamazaki, Richard S. Blumberg, Mamoru Watanabe.
Organizer
United European Gastroenterology Week 2016
Place of Presentation
Austria Center Vienna, Vienna (Austria)
Year and Date
2016-10-19
Related Report
Int'l Joint Research
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[Presentation] Activated B cell receptor signaling may be regulated by CEACAM1.2016
Author(s)
Arisa Tokai, Takashi Nagaishi, Taro Watabe, Nisha Jose, Akinori Hosoya, Motomi Yamazaki, Michio Onizawa, Richard S. Blumberg, Mamoru Watanabe.
Organizer
Federation of Clinical Immunology Societies 2016
Place of Presentation
Seaport Hotel & World Trade Center, Boston (U.S.A.)
Year and Date
2016-06-23
Related Report
Int'l Joint Research
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