c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium.
c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium.
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DOI：
10.1016/j.imbio.2016.09.008
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发表时间：
2017-02
期刊：
影响因子：
2.8
通讯作者：
Mabbott, Neil A.
中科院分区：
文献类型：
--
作者：
Sehgal, Anuj;Kobayashi, Atsushi;Donaldson, David S.;Mabbott, Neil A.
M细胞存在于覆盖在肠道相关淋巴组织上的滤泡相关上皮（FAE）内。这些独特的吞噬上皮细胞使粘膜免疫系统能够在肠腔内取样抗原。在FAE中，M细胞从未确定的前体分化依赖于上皮下基质细胞产生核因子-κB配体受体激活剂（RANKL）。多种细胞表面受体的连接激活核因子-κB （NF-κB）家族转录因子，进而诱导多个靶基因的转录。rankl刺激可刺激NF-κB亚基c-Rel的核易位。因此，我们使用c-Rel缺陷小鼠来确定Peyer 's斑块中M细胞的分化和功能成熟是否依赖于c-Rel。我们的数据显示，c- rel -缺乏不影响Peyer斑块中RANKL或RANK的表达，也不影响FAE中m细胞分化的诱导。在分化的M细胞中，rankl的刺激诱导了SpiB的表达，这对它们随后的成熟至关重要。然而，在没有c-Rel的情况下，FAE中的SpiB表达也不受影响。因此，在c- rel缺陷小鼠的Peyer斑块中，M细胞的功能成熟并未受损。虽然我们的数据显示，在缺乏c-Rel的情况下，FAE中CCL20和泛素D的特异性表达不受阻碍，但在c-Rel缺陷小鼠的B细胞滤泡中，泛素D的表达显著降低。与此相一致的是，我们还观察到，在c- rel缺陷小鼠的Peyer斑块中，B细胞滤泡中的滤泡树突状细胞的状态显着降低。综上所述，我们的数据表明c-Rel对于rankl介导的M细胞分化和功能成熟是必不可少的。
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.
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影响因子：
2.2
作者：
Inman, CF;Rees, LEN;Bailey, M
通讯作者：
Bailey, M
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DOI：
10.1084/jem.20011885
发表时间：
2002-01-21
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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10.1093/dnares/dss022
发表时间：
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期刊：
DNA research : an international journal for rapid publication of reports on genes and genomes
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