The role of NF-kB signaling in intestinal homeostasis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460584
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• 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)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: noncanonical NF-kB / RelB / M cell / Peyer's patch / TRAF6 / Salmonella typhimulium / IgA

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.

Free Research Field

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