The role of NF-kB signaling in intestinal homeostasis
Project/Area Number |
26460584
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Immunology
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Research Institution | Institute of Physical and Chemical Research |
Principal Investigator |
Takashi Kanaya 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (20553829)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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Keywords | noncanonical NF-kB / RelB / M cell / Peyer's patch / TRAF6 / Salmonella typhimulium / IgA / 腸管上皮細胞 / NF-kB / M細胞 / FAE / Spi-B |
Outline of Final Research Achievements |
Canonical NF-κB is involved in the function of intestinal epithelial cells (IECs), however; the role of noncanonical NF-κB in IECs has not been well understood. We found that intestinal M cells exhibit prominent RelB nuclear translocation, which is a marker of noncanonical NF-κB activation. Based on this we evaluated the significance of RelB in M cell development. Organoids established from RelB-deficient mouse could not give rise to M cell upon RANKL administration, suggesting the essential role of noncanonical NF-κB in M cell development. In addition, we evaluated the role of TRAF6, which is essential regulator of RANKL-RANK-mediated NF-κB activation. As we expected, TRAF6-deficient mice exhibited M cell loss in Peyer’s patches. Consistent with this, IgA responses to pathogenic bacterial infection were significantly decreased in TRAF6-deficient mice compared to control mice. Our study demonstrates that TRAF6-mediated noncanonical NF-κB is essential for M cell development.
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] IL-22BP dictates characteristics of Peyer’s patch follicle-associated epithelium for antigen uptake.2017
Author(s)
Toshi Jinnohara, Takashi Kanaya, Koji Hase, Sayuri Sakakibara, Tamotsu Kato, Naoko Tachibana, Takaharu Sasaki, Yusuke Hashimoto, Toshiro Sato, Hiroshi Watarai, Jun Kunisawa, Naoko Shibata, Ifor R Williams, Hiroshi Kiyono, and Hiroshi Ohno.
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Journal Title
Journal of Experimental Medicine
Volume: 印刷中
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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