c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium

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• 作者：Anuj Sehgal^a ; Atsushi Kobayashi^b ; David S. Donaldson^a ; Neil A. Mabbott^a ; ^{neil.mabbott@roslin.ed.ac.uk}
• 关键词：Anxa5 ; annexin A5 ; FAE ; follicle-associated epithelium ; FDC ; follicular dendritic cell ; GALT ; gut-associated lymphoid tissues ; IHC ; immunohistochemistry ; Marcksl1 ; myristoylated alanine-rich C-kinase substrate-like protein 1 ; NF-κB ; nuclear factor-κB ; RANK ; receptor activator of nuclear factor-κB ; RANKL ; receptor activator of nuclear factor-κB ligand ; Scg5 ; secretogranin V ; SED ; sub-epithelial dome ; LT ; lymphotoxin ; UBD ; ubiquitin D ; UEA-1 ; Ulex europaeus agglutinin-1
• 刊名：Immunobiology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：222
• 期：2
• 页码：316-326
• 全文大小：4958 K
• 卷排序：222

文摘

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-κB ligand (RANKL) by subepithelial stromal cells. The ligation of a variety of cell surface receptors activates the nuclear factor-κB (NF-κB) family of transcription factors which in-turn induce the transcription of multiple target genes. RANKL-stimulation can stimulate the nuclear translocation of the NF-κB subunit c-Rel. We therefore used c-Rel-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.