Abstract：
BACKGROUND: The Th2 cell polarization is a crucial factor in the pathogenesis of allergic diseases. The underlying mechanism requires further investigation. Telomerase has an immune-regulating ability. The aim of this study is to elucidate the association between telomerase and Th2 cell polarization in patients with allergic rhinitis (AR).
METHODS: CD4+ T cells were isolated from blood samples collected from AR patients and healthy control subjects. RNA sequencing was employed to analyze RNA samples extracted from CD4+ T cells. An AR mouse model was established using the ovalbumin-alum protocol.
RESULTS: High telomerase gene activity and high endoplasmic reticulum (ER) stress status were observed in CD4+ T-cells in patients with AR. Positive correlation between the telomerase reverse transcriptase (TERT) gene expression in CD4+ T cells and AR response in patients with AR. TERT facilitated the degradation of Foxp3 proteins in CD4+ T cells, resulting in the polarization of Th2 cells. Sensitization with the ovalbumin-alum protocol enhanced the Tert expression in CD4+ T cells by exacerbating ER stress. Conditional inhibition of the Tert or eukaryotic translation initiation factor 2-α (Eif2a) expression in CD4+ T cells effectively attenuated experimental AR in mice.
CONCLUSIONS: Elevated amounts of telomerase in CD4+ T cells were found in CD4+ T cells of subjects with AR. Telomerase promoted Th2 cell polarization by inducing Foxp3 protein degradation and promotes GATA3 activation. Inhibition of TERT or eIF2a alleviated experimental AR.
METHODS: CD4+ T cells were isolated from blood samples collected from AR patients and healthy control subjects. RNA sequencing was employed to analyze RNA samples extracted from CD4+ T cells. An AR mouse model was established using the ovalbumin-alum protocol.
RESULTS: High telomerase gene activity and high endoplasmic reticulum (ER) stress status were observed in CD4+ T-cells in patients with AR. Positive correlation between the telomerase reverse transcriptase (TERT) gene expression in CD4+ T cells and AR response in patients with AR. TERT facilitated the degradation of Foxp3 proteins in CD4+ T cells, resulting in the polarization of Th2 cells. Sensitization with the ovalbumin-alum protocol enhanced the Tert expression in CD4+ T cells by exacerbating ER stress. Conditional inhibition of the Tert or eukaryotic translation initiation factor 2-α (Eif2a) expression in CD4+ T cells effectively attenuated experimental AR in mice.
CONCLUSIONS: Elevated amounts of telomerase in CD4+ T cells were found in CD4+ T cells of subjects with AR. Telomerase promoted Th2 cell polarization by inducing Foxp3 protein degradation and promotes GATA3 activation. Inhibition of TERT or eIF2a alleviated experimental AR.
摘要：
背景：Th2细胞极化是过敏性疾病发病的关键因素。潜在的机制需要进一步调查。端粒酶具有免疫调节能力。这项研究的目的是阐明端粒酶与过敏性鼻炎（AR）患者Th2细胞极化之间的关系。
方法：从AR患者和健康对照受试者的血液样品中分离CD4+T细胞。采用RNA测序来分析从CD4+T细胞提取的RNA样品。使用卵清蛋白-明矾方案建立AR小鼠模型。
结果：在AR患者的CD4T细胞中观察到高端粒酶基因活性和高内质网（ER）应激状态。CD4+T细胞端粒酶逆转录酶(TERT)基因表达与AR患者AR反应呈正相关。TERT促进CD4+T细胞中Foxp3蛋白的降解,导致Th2细胞的极化。卵清蛋白-明矾方案的敏化通过加剧ER应激来增强CD4+T细胞中的Tert表达。CD4T细胞中Tert或真核翻译起始因子2-α（Eif2a）表达的条件性抑制可有效减弱小鼠的实验性AR。
结论：在AR患者的CD4+T细胞中发现CD4+T细胞中端粒酶的含量升高。端粒酶通过诱导Foxp3蛋白降解促进Th2细胞极化并促进GATA3活化。TERT或eIF2a的抑制减轻了实验性AR。
方法：从AR患者和健康对照受试者的血液样品中分离CD4+T细胞。采用RNA测序来分析从CD4+T细胞提取的RNA样品。使用卵清蛋白-明矾方案建立AR小鼠模型。
结果：在AR患者的CD4T细胞中观察到高端粒酶基因活性和高内质网（ER）应激状态。CD4+T细胞端粒酶逆转录酶(TERT)基因表达与AR患者AR反应呈正相关。TERT促进CD4+T细胞中Foxp3蛋白的降解,导致Th2细胞的极化。卵清蛋白-明矾方案的敏化通过加剧ER应激来增强CD4+T细胞中的Tert表达。CD4T细胞中Tert或真核翻译起始因子2-α（Eif2a）表达的条件性抑制可有效减弱小鼠的实验性AR。
结论：在AR患者的CD4+T细胞中发现CD4+T细胞中端粒酶的含量升高。端粒酶通过诱导Foxp3蛋白降解促进Th2细胞极化并促进GATA3活化。TERT或eIF2a的抑制减轻了实验性AR。
