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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Human uterine epithelial cell secretions regulate dendritic cell differentiation and responses to TLR ligands
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Human uterine epithelial cell secretions regulate dendritic cell differentiation and responses to TLR ligands

机译:人子宫上皮细胞分泌调节树突状细胞分化和对TLR配体的反应

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The balance between immunity and tolerance in the endometrium is governed by dynamic interactions of UEC and immune cells including DC. In this study, we tested the hypothesis that soluble immune mediators secreted by UEC modulate the differentiation and functions of human DC. We found that DC differentiated with CM from polarized UEC (i.e., CM-DC) expressed significantly lower surface CD86. Upon activation with LPS or PIC, the expression of CD80, CD86, and CD83 was decreased significantly on CM-DC relative to Con-DC. Further, mRNA for TLR3, TLR4, and TLR5 was decreased significantly in CM-DC relative to Con-DC. As a functional read-out of the effect of CM on DC, we determined the following parameters: First, analysis of cytokine production showed that when compared with Con-DC, CM-DC responded to LPS or PIC stimulation with enhanced IL-10 production but undetectable IL-12p70 secretion. Second, RT-PCR analysis showed that CM-DC significantly expressed higher mRNA for IDO, an immune tolerance-promoting enzyme. Lastly, in a MLR assay, CM-DC induced significantly lower allogeneic proliferative responses compared with Con-DC. These findings indicate collectively that epithelial cells confer a tolerogenic phenotype to DC in the endometrium. Our results suggest novel cellular and molecular mechanisms for the regulation of adaptive immunity within the FRT.
机译:子宫内膜的免疫力和耐受性之间的平衡受UEC与包括DC在内的免疫细胞动态相互作用的支配。在这项研究中,我们测试了UEC分泌的可溶性免疫介质调节人DC分化和功能的假说。我们发现与极化UEC(即CM-DC)的CM区分的DC表达了明显较低的表面CD86。通过LPS或PIC激活后,相对于Con-DC,CM-DC上CD80,CD86和CD83的表达显着降低。此外,相对于Con-DC,CM-DC中TLR3,TLR4和TLR5的mRNA显着降低。作为对CM对DC影响的功能性读数,我们确定了以下参数:首先,对细胞因子产生的分析表明,与Con-DC相比,CM-DC对LPS或PIC刺激具有增强的IL-10产生反应但无法检测到IL-12p70分泌。其次,RT-PCR分析表明CM-DC明显表达了IDO(一种促进免疫耐受的酶)的更高mRNA。最后,在MLR分析中,与Con-DC相比,CM-DC诱导的同种异体增殖反应明显降低。这些发现共同表明,上皮细胞向子宫内膜的DC赋予耐受性表型。我们的研究结果表明新型的细胞和分子机制来调节FRT内的适应性免疫。

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