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

研究成果: Article査読

31 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)501-519
ページ数19
ジャーナルJournal of Experimental Medicine
215
2
DOI
出版ステータスPublished - 2018 2 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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