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Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling
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 differentiat...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789402/ https://www.ncbi.nlm.nih.gov/pubmed/29339448 http://dx.doi.org/10.1084/jem.20160659 |
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author | 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 |
author_facet | 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 |
author_sort | Kanaya, Takashi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5789402 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57894022018-08-05 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 J Exp Med Research Articles 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. The Rockefeller University Press 2018-02-05 /pmc/articles/PMC5789402/ /pubmed/29339448 http://dx.doi.org/10.1084/jem.20160659 Text en © 2018 Kanaya et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles 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 |
title | Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling |
title_full | Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling |
title_fullStr | Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling |
title_full_unstemmed | Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling |
title_short | Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling |
title_sort | development of intestinal m cells and follicle-associated epithelium is regulated by traf6-mediated nf-κb signaling |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789402/ https://www.ncbi.nlm.nih.gov/pubmed/29339448 http://dx.doi.org/10.1084/jem.20160659 |
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