RRC ID 50038
Author 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.
Title Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling.
Journal J Exp Med
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.
Volume 215(2)
Pages 501-519
Published 2018-2-5
DOI 10.1084/jem.20160659
PII jem.20160659
PMID 29339448
PMC PMC5789402
MeSH Animals Cell Differentiation Cell Lineage Humans Intestinal Mucosa / cytology* Intestinal Mucosa / immunology* Intestinal Mucosa / metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout NF-kappa B / metabolism* Organoids / cytology Organoids / immunology Organoids / metabolism Peyer's Patches / cytology Peyer's Patches / immunology Peyer's Patches / metabolism RANK Ligand / metabolism Receptor Activator of Nuclear Factor-kappa B / metabolism Signal Transduction TNF Receptor-Associated Factor 6 / deficiency TNF Receptor-Associated Factor 6 / genetics TNF Receptor-Associated Factor 6 / metabolism*
IF 10.892
Times Cited 24
DNA material CSII-CMV-RfA-IRES2-Venus (RDB04388) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393).