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Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling

Takashi Kanaya1,2, Sayuri Sakakibara1, Toshi Jinnohara1,2

  • 1Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.

The Journal of Experimental Medicine
|January 18, 2018
PubMed

Insights

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is crucial for M cell development in Peyer's patches. Its absence leads to a complete loss of M cells and impaired intestinal antigen uptake.

Area of Science:

  • Immunology
  • Gastroenterology
  • Cell Biology

Background:

  • M cells in Peyer's patches (PPs) facilitate intestinal antigen uptake.
  • M cell differentiation is initiated by receptor activator of NF-κB (RANK), but intracellular pathways remain unclear.

Purpose of the Study:

  • To elucidate the intracellular signaling pathways governing M cell differentiation.
  • To investigate the role of tumor necrosis factor receptor-associated factor 6 (TRAF6) in M cell development.

Main Methods:

  • In vitro organoid culture to study M cell differentiation.
  • Conditional deletion of TRAF6 in the intestinal epithelium of mice.
  • Analysis of M cell-associated molecules and FAE-associated genes.

Main Results:

  • RANK-activated NF-κB signaling is essential for M cell differentiation.
  • Overexpression of NF-κB factors enhances M cell markers but doesn't complete differentiation.
  • Conditional deletion of TRAF6 abrogates M cell development in PPs and silences FAE gene expression.

Conclusions:

  • TRAF6 is indispensable for M cell differentiation and follicle-associated epithelium (FAE) development.
  • TRAF6-mediated NF-κB signaling is a critical pathway for M cell formation and function.
  • Loss of TRAF6 severely impairs intestinal antigen sampling due to M cell deficiency.

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