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首页> 外文期刊>Allergy >Enhanced glucocorticoid-induced leucine zipper in dendritic cells induces allergen-specific regulatory CD4+T-cells in respiratory allergies
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Enhanced glucocorticoid-induced leucine zipper in dendritic cells induces allergen-specific regulatory CD4+T-cells in respiratory allergies

机译:树突状细胞中增强的糖皮质激素诱导的亮氨酸拉链诱导呼吸道过敏中的过敏原特异性调节性CD4 + T细胞

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Background: Respiratory allergies rely on a defect of IL-10-secreting regulatory CD4+T-cells (IL-10-Tregs) leading to excessive Th2-biased immune responses to allergens. According to clinical data, the restoration of allergen-specific IL-10-Tregs is required to control respiratory allergies and cure patients. The discovery of mechanisms involved in the generation of IL-10-Tregs will thus help to provide effective treatments. We previously demonstrated that dendritic cells (DCs) expressing high levels of the glucocorticoid-induced leucine zipper protein (GILZ) generate antigen-specific IL-10-Tregs. Objective We suspect a defective expression of GILZ in the DCs of respiratory allergic patients and speculate that increasing its expression might restore immune tolerance against allergens through the induction of IL-10-Tregs. Methods: We assessed GILZ expression in blood DCs of patients and healthy nonallergic donors by qPCR. We compared the ability of patients' DCs to induce allergen-specific IL-10-T regs before and after an in vivo up-regulation of GILZ expression by steroid administration, steroids being inducers of GILZ. Results We report lower levels of GILZ in DCs of respiratory allergic patients that return to normal levels after steroid administration. We show that patients' DCs with increased levels of GILZ generate allergen-specific IL-10-Tregs again. We further confirm unequivocally that GILZ is required in patients' DCs to activate these IL-10-Tregs. Conclusion This proof of concept study shows that the re-establishment of GILZ expression in patients' DCs to normal levels restores their capacity to activate allergen-specific IL-10-Tregs. We thus highlight the up-regulation of GILZ in DCs as a new interventional approach to restore the immune tolerance to allergens.
机译:背景:呼吸道过敏依赖于分泌IL-10-的调节性CD4 + T细胞(IL-10-Tregs)的缺陷,导致对过敏原的Th2偏向过度的免疫反应。根据临床数据,需要恢复过敏原特异性的IL-10-Treg,以控制呼吸道过敏和治愈患者。因此,与IL-10-Tregs产生有关的机制的发现将有助于提供有效的治疗方法。我们以前证明树突状细胞(DCs)表达高水平的糖皮质激素诱导的亮氨酸拉链蛋白(GILZ)生成抗原特异性IL-10-Tregs。目的我们怀疑呼吸道过敏患者DC中GILZ的表达有缺陷,并推测增加其表达可能通过诱导IL-10-Tregs恢复对变应原的免疫耐受。方法:我们通过qPCR评估了患者和健康非过敏性供体血液DC中GILZ的表达。我们比较了通过类固醇给药在体内上调GILZ表达前后,患者DC诱导过敏原特异性IL-10-T regs的能力,类固醇是GILZ的诱导剂。结果我们报告了在类固醇给药后恢复正常水平的呼吸道过敏患者DC中的GILZ水平较低。我们表明,患者的DC的GILZ水平升高,再次产生了过敏原特异性的IL-10-Treg。我们进一步明确证实,患者DC中需要GILZ才能激活这些IL-10-Treg。结论这项概念验证研究表明,患者DC中GILZ表达的恢复可恢复至正常水平,从而恢复了其激活过敏原特异性IL-10-Treg的能力。因此,我们强调了DC中GILZ的上调作为恢​​复对过敏原的免疫耐受的新干预方法。

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