Cargando…

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...

Descripción completa

Detalles Bibliográficos
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
Descripción
Sumario: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.