MicroRNA-100-5p indirectly modulates the expression of Il6, Ptgs1/2 and Tlr4 mRNA in the mouse follicular dendritic cell-like cell line, FL-Y.

MicroRNA-100-5p indirectly modulates the expression of Il6, Ptgs1/2 and Tlr4 mRNA in the mouse follicular dendritic cell-like cell line, FL-Y.
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DOI:
10.1111/imm.12342
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发表时间:
2015-01
期刊:
影响因子:
6.4
通讯作者:
Mabbott NA
Mabbott NA
中科院分区:
医学2区
文献类型:
--
作者:
Aungier SR;Ohmori H;Clinton M;Mabbott NA

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滤泡树突状细胞(FDC)是次级淋巴组织的B细胞滤泡和生发中心(GC)内重要的基质细胞。FDC以免疫复合物的形式捕获并在其表面保留天然抗原,将其展示给B细胞,以便筛选出具有最高抗原亲和力的细胞。微小RNA是短的非编码RNA,长度约为18 - 25个核苷酸,通过抑制靶基因的翻译在转录后水平调节基因表达。在当前的研究中,利用体内和体外系统来鉴定FDC可能表达的微小RNA。组成性淋巴毒素 - β受体(LTβR)刺激是维持FDC分化状态所必需的。我们发现,伴随LTβR阻断,脾脏FDC迅速去分化,同时mmu - miR - 100 - 5p、mmu - miR - 138 - 5p和mmu - miR - 2137的表达显著降低。这些微小RNA在FDC样细胞系FL - YB中表达,并且对mmu - miR - 100 - 5p的特异性抑制显著增强了该细胞系中Il6、Ptgs1/2和Tlr4 mRNA的表达。FDC表达的Il6、Ptgs1/2和Tlr4在调节生发中心大小和促进高亲和力抗体反应中起重要作用,因此mmu - miR - 100 - 5p可能有助于在生发中心反应期间调节这些基因的表达是合理的。
Follicular dendritic cells (FDC) are important stromal cells within the B-cell follicles and germinal centres (GC) of secondary lymphoid tissues. FDC trap and retain native antigens on their surfaces in the form of immune complexes that they display to B cells, in order to select those cells with the highest antigen affinity. MicroRNAs are short, non-coding RNAs that are approximately 18–25 nucleotides in length that regulate gene expression at the post-transcriptional level by repressing the translation of target genes. In the current study, in vivo and in vitro systems were used to identify microRNAs that were potentially expressed by FDC. Constitutive lymphotoxin-β receptor (LTβR) stimulation is required to maintain FDC in their differentiated state. We show that the rapid de-differentiation of spleen FDC that accompanied LTβR-blockade, coincided with a significant decrease in the expression of mmu-miR-100-5p, mmu-miR-138-5p and mmu-miR-2137. These microRNAs were shown to be expressed in the FDC-like cell line, FL-YB, and specific inhibition of mmu-miR-100-5p significantly enhanced expression of Il6, Ptgs1/2 and Tlr4 mRNA in this cell line. The expression of Il6, Ptgs1/2 and Tlr4 by FDC play important roles in regulating GC size and promoting high-affinity antibody responses, so it is plausible that mmu-miR-100-5p may help to regulate the expression of these genes during GC reactions.
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