Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands.
Int Arch Allergy Immunol. 2013;162(3):225-36. doi: 10.1159/000353243. Epub 2013 Sep 6.
Non-inflammatory dendritic cell (DC) subsets play an essential role in preventing massive inflammation in mucosal tissues. We investigated whether mucosa-related factors, namely retinoic acid (RA) and transforming growth factor-β (TGF-β1), can induce such DC types. DCs were differentiated from monocytes in the absence or presence TGF-β1 and RA. The phenotype as well as responsiveness to bacterial ligands was studied in detail. Compared to monocyte-derived DCs (moDCs), the expression of co-stimulatory molecule CD86 and DC maturation marker CD83 were strongly reduced by RA and TGF-β1. In addition, both RA- and TGF-β1-induced DCs showed strongly decreased responsiveness to stimulation with the bacterial ligands lipopolysaccharide and peptidoglycan, and produced significantly lower levels of the pro-inflammatory cytokines IL-12 and TNF-α compared to moDCs, whilst IL-10 production was not significantly reduced. DCs differentiated under the influence of RA uniquely expressed markers related to intestinal homing (CD103 and integrin β7). In addition, CCR7, which mediates homing to lymph nodes, was expressed by DCs differentiated in the presence of RA, and also to a lesser extent by the other DC types. Furthermore, whereas moDCs and TGF-β1-derived moDCs expressed high levels of CD32, RA-derived DCs lacked CD32 expression but expressed high levels of CD64, suggesting that RA-DCs may primarily respond to soluble proteins and moDCs, and TGF-β DCs to immune complexes. The data presented here support the hypothesis that the mucosal factors TGF-β1 and RA, which can also be provided through dietary intake of dairy products, result in functionally and phenotypically distinct DC types with non-inflammatory properties.
非炎症性树突状细胞（DC）亚群在防止黏膜组织发生大规模炎症中发挥着重要作用。我们研究了黏膜相关因子，即视黄酸（RA）和转化生长因子-β（TGF-β1），是否可以诱导这种 DC 类型。我们在有无 TGF-β1 和 RA 的情况下从单核细胞中分化 DC。详细研究了 DC 的表型以及对细菌配体的反应性。与单核细胞来源的 DC（moDCs）相比，RA 和 TGF-β1 强烈降低了共刺激分子 CD86 和 DC 成熟标志物 CD83 的表达。此外，RA 和 TGF-β1 诱导的 DC 对细菌配体脂多糖和肽聚糖的刺激反应性均明显降低，与 moDCs 相比，促炎细胞因子 IL-12 和 TNF-α 的产生水平明显降低，而 IL-10 的产生水平没有明显降低。在 RA 影响下分化的 DC 独特地表达与肠道归巢相关的标志物（CD103 和整合素β7）。此外，介导归巢至淋巴结的 CCR7 在 RA 存在下分化的 DC 中表达，在其他 DC 类型中也有表达，但程度较低。此外，虽然 moDCs 和 TGF-β1 衍生的 moDCs 表达高水平的 CD32，但 RA 衍生的 DCs 缺乏 CD32 表达，但表达高水平的 CD64，这表明 RA-DCs 可能主要对可溶性蛋白和 moDCs 作出反应，而 TGF-β DCs 则对免疫复合物作出反应。本文提供的数据支持了这样一种假设，即黏膜因子 TGF-β1 和 RA 也可以通过摄入乳制品来提供，从而产生具有非炎症特性的功能和表型不同的 DC 类型。
