期刊
IMMUNOBIOLOGY
卷 222, 期 2, 页码 316-326出版社
ELSEVIER GMBH
DOI: 10.1016/j.imbio.2016.09.008
关键词
c-Rel; M cells; Follicle-associated epithelium; Peyer's patches; RANKL
类别
资金
- Biotechnology and Biological Sciences Research Council [BB/J014672/1, BB/J004227/1, BBS/E/D/20231762, BB/J01446X/1]
- Japan Society for the Promotion of Science Fellowship for Research Abroad
- Mitsubishi Foundation
- Biotechnology and Biological Sciences Research Council [1267506, BB/K021257/1, BBS/E/D/20231759, BB/J014672/1] Funding Source: researchfish
- BBSRC [BB/J014672/1, BBS/E/D/20231759, BB/K021257/1] Funding Source: UKRI
- Grants-in-Aid for Scientific Research [16K18790] Funding Source: KAKEN
M cells reside within the follicle-associated epithelium (FAE) overlying the gut-associated lymphoid tissues. These unique phagocytic epithelial cells enable the mucosal immune system to sample antigens within the lumen of the intestine. The differentiation of M cells from uncommitted precursors in the FAE is dependent on the production of receptor activator of nuclear factor-KB ligand (RANKL) by subepithelial stromal cells. The ligation of a variety of cell surface receptors activates the nuclear factor-kappa B (NF-kappa B) family of transcription factors which in-turn induce the transcription of multiple target genes. RANKL-stimulation can stimulate the nuclear translocation of the NF-kappa B subunit c-Rel. We therefore used cRel-deficient mice to determine whether the differentiation and functional maturation of M cells in the Peyer's patches was dependent on c-Rel. Our data show that c-Rel-deficiency does not influence the expression of RANKL or RANK in Peyer's patches, or the induction of M-cell differentiation in the FAE. RANKL-stimulation in the differentiating M cells induces the expression of SpiB which is essential for their subsequent maturation. However, SpiB expression in the FAE was also unaffected in the absence of c-Rel. As a consequence, the functional maturation of M cells was not impaired in the Peyer's patches of c-Rel-deficient mice. Although our data showed that the specific expression of CCL20 and ubiquitin D in the FAE was not impeded in the absence of c-Rel, the expression of ubiquitin D was dramatically reduced in the B cell-follicles of c-Rel-deficient mice. Coincident with this, we also observed that the status of follicular dendritic cells in the B cell-follicles was dramatically reduced in Peyer's patches from c-Rel-deficient mice. Taken together, our data show that c-Rel is dispensable for the RANKL-mediated differentiation and functional maturation of M cells. (C) 2016 The Authors. Published by Elsevier GmbH.
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