期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 215, 期 2, 页码 501-519出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20160659
关键词
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资金
- Japan Society for the Promotion of Science KAKENHI [26460584, 24249029]
- Ministry of Education, Culture, Sports, Science and Technology KAKENHI [15H01165, 20113003]
- Uehara Memorial Foundation
- Takeda Science Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Grants-in-Aid for Scientific Research [16H05207, 17H06176, 15H01165, 26115007, 16H01631] Funding Source: KAKEN
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-kappa B. However, the intracellular pathways involved in M cell differentiation are still elusive. In this study, we demonstrate that the NF-kappa B pathway activated by RANK is essential for M cell differentiation using in vitro organoid culture. Overexpression of NF-kappa 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-kappa B signaling in the development of M cells and FAE.
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