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

Takashi Kanaya, Sayuri Sakakibara, Toshi Jinnohara, Masami Hachisuka, Naoko Tachibana, Shinya Hidano, Takashi Kobayashi, Shunsuke Kimura, Toshihiko Iwanaga, Tomoo Nakagawa, Tatsuro Katsuno, Naoya Kato, Taishin Akiyama, Toshiro Sato, Ifor R. Williams, Hiroshi Ohno

Research output: Contribution to journalArticle

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Abstract

M cells are located in the follicle-associated epithelium (FAE) that covers Peyer's patches (PPs) and are responsible for the uptake of intestinal antigens. The differentiation of M cells is initiated by receptor activator of NF-κB. However, the intracellular pathways involved in M cell differentiation are still elusive. In this study, we demonstrate that the NF-κB pathway activated by RANK is essential for M cell differentiation using in vitro organoid culture. Overexpression of NF-κB transcription factors enhances the expression of M cell-associated molecules but is not sufficient to complete M cell differentiation. Furthermore, we evaluated the requirement for tumor necrosis factor receptor-associated factor 6 (TRAF6). Conditional deletion of TRAF6 in the intestinal epithelium causes a complete loss of M cells in PPs, resulting in impaired antigen uptake into PPs. In addition, the expression of FAE-associated genes is almost silenced in TRAF6-deficient mice. This study thus demonstrates the crucial role of TRAF6-mediated NF-κB signaling in the development of M cells and FAE.

Original languageEnglish
Pages (from-to)501-519
Number of pages19
JournalJournal of Experimental Medicine
Volume215
Issue number2
DOIs
Publication statusPublished - 2018 Feb 1

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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Peyer's Patches
Cell Differentiation
Epithelium
Organoids
Antigens
Intestinal Mucosa
Transcription Factors
Genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kanaya, T., Sakakibara, S., Jinnohara, T., Hachisuka, M., Tachibana, N., Hidano, S., ... Ohno, H. (2018). Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling. Journal of Experimental Medicine, 215(2), 501-519. https://doi.org/10.1084/jem.20160659

Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling. / Kanaya, Takashi; Sakakibara, Sayuri; Jinnohara, Toshi; Hachisuka, Masami; Tachibana, Naoko; Hidano, Shinya; Kobayashi, Takashi; Kimura, Shunsuke; Iwanaga, Toshihiko; Nakagawa, Tomoo; Katsuno, Tatsuro; Kato, Naoya; Akiyama, Taishin; Sato, Toshiro; Williams, Ifor R.; Ohno, Hiroshi.

In: Journal of Experimental Medicine, Vol. 215, No. 2, 01.02.2018, p. 501-519.

Research output: Contribution to journalArticle

Kanaya, T, Sakakibara, S, Jinnohara, T, Hachisuka, M, Tachibana, N, Hidano, S, Kobayashi, T, Kimura, S, Iwanaga, T, Nakagawa, T, Katsuno, T, Kato, N, Akiyama, T, Sato, T, Williams, IR & Ohno, H 2018, 'Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling', Journal of Experimental Medicine, vol. 215, no. 2, pp. 501-519. https://doi.org/10.1084/jem.20160659
Kanaya, Takashi ; Sakakibara, Sayuri ; Jinnohara, Toshi ; Hachisuka, Masami ; Tachibana, Naoko ; Hidano, Shinya ; Kobayashi, Takashi ; Kimura, Shunsuke ; Iwanaga, Toshihiko ; Nakagawa, Tomoo ; Katsuno, Tatsuro ; Kato, Naoya ; Akiyama, Taishin ; Sato, Toshiro ; Williams, Ifor R. ; Ohno, Hiroshi. / Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling. In: Journal of Experimental Medicine. 2018 ; Vol. 215, No. 2. pp. 501-519.
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