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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2018
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.
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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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