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首页> 外文期刊>Allergy >Tolerogenic T cells, Th1/Th17 cytokines and TLR2/TLR4 expressing dendritic cells predominate the microenvironment within distinct oral mucosal sites.
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Tolerogenic T cells, Th1/Th17 cytokines and TLR2/TLR4 expressing dendritic cells predominate the microenvironment within distinct oral mucosal sites.

机译：耐受性T细胞，表达Th1 / Th17的细胞因子和TLR2 / TLR4表达的树突状细胞在不同的口腔粘膜位点内占据着微环境。

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摘要

BACKGROUND: Most local oral vaccine strategies use the sublingual region for drug application. Only little is known about the cytokine micromilieu, the nature of T cell subtypes and expression of target structures for adjuvants at different oral mucosal regions (OMR). However, targeting the optimal OMR might ensure highest efficiency of drug uptake and lowest risk for adverse effects. METHODS: Expression of TGF-beta1, IL10 as well as Th1, Th2 and Th17 cytokines and transcription factors was investigated at different OMR and skin by quantitative real-time PCR, immunohistochemistry or flow cytometry. RESULTS: Highest number of T cells was located in vestibular/buccal region (VBR). In contrast to skin (SK), OMR T cells produced TGF-beta1, IL-10, IFN-gamma and IL-17. Significantly higher TGF-beta1 mRNA expression in the VBR compared with the sublingual region (SLR) and skin could be detected, while equal transcripts of IL-10 and regulatory T cell-associated transcription factor FoxP3 could be demonstrated. Expression of Th17-associated IL-17A, IL-17F, IL-22 and IL-26 mRNA could be demonstrated in VBR and SLR but not in SK. Interestingly, compared to SK, significantly higher expression of TGF-beta1 and IFN-gamma could be detected in OMR. Moreover, expression of toll-like receptor (TLR) 2 and TLR4 was highest in VBR with significant expression on dendritic cells in OMR. CONCLUSION: From this data, we conclude that (i) VBR and SLR represent a protolerogenic micromilieu, (ii) both regions form a Th1 cytokine-predominated microenvironment, but also express mRNA for Th17 cytokines and (iii) TLRs detectable in VBR and SLR might serve as a target structures for adjuvants.
机译：背景：大多数局部口服疫苗策略使用舌下区域进行药物应用。关于细胞因子的微环境，T细胞亚型的性质以及佐剂在不同口腔粘膜区域（OMR）的靶标结构的表达知之甚少。但是，针对最佳OMR可以确保最高的药物吸收效率和最低的不良反应风险。方法：采用定量实时荧光定量PCR，免疫组织化学或流式细胞术研究了不同OMR和皮肤中TGF-β1，IL10以及Th1，Th2和Th17细胞因子和转录因子的表达。结果：T细胞数量最多的位于前庭/颊区（VBR）。与皮肤（SK）相反，OMR T细胞产生TGF-beta1，IL-10，IFN-γ和IL-17。与舌下区域（SLR）和皮肤相比，可以检测到VBR中的TGF-beta1 mRNA表达明显更高，而IL-10和调节性T细胞相关转录因子FoxP3的转录本却相等。 Th17相关的IL-17A，IL-17F，IL-22和IL-26 mRNA的表达可以在VBR和SLR中得到证实，而在SK中则没有。有趣的是，与SK相比，可以在OMR中检测到TGF-beta1和IFN-γ的明显更高的表达。此外，Toll样受体（TLR）2和TLR4的表达在VBR中最高，在OMR中的树突状细胞上也有明显表达。结论：根据这些数据，我们得出结论：（i）VBR和SLR代表致原性微环境;（ii）两个区域均形成以Th1细胞因子为主的微环境，但也表达Th17细胞因子的mRNA;（iii）在VBR和SLR中可检测到的TLR可能用作佐剂的目标结构。

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