First Author | Kanaya T | Year | 2018 |
Journal | J Exp Med | Volume | 215 |
Issue | 2 | Pages | 501-519 |
PubMed ID | 29339448 | Mgi Jnum | J:257471 |
Mgi Id | MGI:6119933 | Doi | 10.1084/jem.20160659 |
Citation | Kanaya T, et al. (2018) Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-kappaB signaling. J Exp Med 215(2):501-519 |
abstractText | 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-kappaB. However, the intracellular pathways involved in M cell differentiation are still elusive. In this study, we demonstrate that the NF-kappaB pathway activated by RANK is essential for M cell differentiation using in vitro organoid culture. Overexpression of NF-kappaB 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-kappaB signaling in the development of M cells and FAE. |