Yan Feng, Zhishou Zhang, Hui Huangfu, Haiyang Han, Bailing Xie, Shuo Song, Tao Liu, Yunfang An, Pingchang Yang
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引用次数: 0
摘要
过敏原特异性免疫疗法(AIT)是一种针对过敏性疾病的病原学疗法。过敏原特异性免疫疗法的治疗机制尚未完全明了。内质网应激与过敏性疾病的发病机制有关。本研究旨在阐明 AIT 通过调节内质网应激抑制过敏反应的作用。本研究招募了常年过敏性鼻炎患者。对患者进行了 AIT 治疗。以螨虫提取物为过敏原,建立了过敏性鼻炎(AR)小鼠模型。我们发现,AIT 可调节过敏性鼻炎患者外周 CD4+ T 细胞的内质网应激状态。AIT 上调了 CD4+ T 细胞中与 PERK(蛋白激酶 RNA 样内质网激酶)-eIF2a(真核翻译起始因子 2a)轴相关的内质网应激强度,这与 AIT 后过敏性鼻炎反应的改善密切相关。AIT 疫苗中的高剂量氢氧化铝(明矾)增强了 XBP1 抑制 CD4+ T 细胞中 eIF2a 的活性。含有低剂量明矾的 AIT 能有效缓解实验性过敏性鼻炎,而不含明矾或高剂量明矾的 AIT 则会加重实验性过敏性鼻炎。总之,过敏原疫苗中的明矾佐剂可以调节 eIF2a 的活性,从而调节 CD4+ T 细胞中 Th2 细胞因子的表达。调节过敏原疫苗中明矾的剂量有可能增强过敏原疫苗的治疗效果。
Adjuvant alum regulates the eIF2a-GATA3 axis in CD4+ T cells to influence allergen immunotherapy.
Allergen-specific immunotherapy (AIT) is an aetiology-targeting therapy for allergic diseases. The therapeutic mechanism of AIT is not fully understood yet. Endoplasmic reticulum stress is associated with the pathogenesis of allergic disorders. This study aims to elucidate the effects of AIT on suppressing allergic response through regulating endoplasmic reticulum stress. In this study, patients with perennial allergic rhinitis were recruited. AIT was conducted for the patients. An allergic rhinitis (AR) mouse model was established with mite extracts as allergens. We found that AIT modulated the endoplasmic reticulum stress status in peripheral CD4+ T cells in patients with allergic rhinitis. The intensity of endoplasmic reticulum stress associated the PERK (protein kinase RNA-like endoplasmic reticulum kinase)-eIF2a (eukaryotic translation initiation factor 2a) axis in CD4+ T cells was upregulated by AIT, which was closely associated with the improvement in allergic rhinitis response after AIT. eIF2a interacted with GATA3 to downregulate the IL4 gene transcription in CD4+ T cells. High doses of aluminium hydroxide (alum) in AIT vaccines enhanced the activity of XBP1 to suppress eIF2a in CD4+ T cells. AIT containing a low dose of alum effectively mitigated the experimental allergic rhinitis, while the AIT without alum or a high dose of alum exacerbated the experimental allergic rhinitis. In conclusion, the alum adjuvant in allergen vaccines can regulate the activity of eIF2a to regulate the expression of Th2 cytokines in CD4+ T cells. Manipulating the alum dose in AIT vaccines has the potential to enhance the therapeutic effects of AIT.
期刊介绍:
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