Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-?B signaling.

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-?B. However, the intracellular pathways involved in M cell differentiation are still elusive. In this study, we demonstrate that the NF-?B pathway activated by RANK is essential for M cell differentiation using in vitro organoid culture. Overexpression of NF-?B 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-?B signaling in the development of M cells and FAE.

SUBMITTER: Kanaya T 

PROVIDER: S-EPMC5789402 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature