Immunopharmacology and Immunotoxicology ( IF 3.3 ) Pub Date : 2020-12-07 , DOI: 10.1080/08923973.2020.1850762 Yuqin Fan 1 , Chenchen Yang 2 , Jieyu Zhou 1 , Xuefeng Cheng 1 , Yu Dong 1 , Qin Wang 1 , Zhentao Wang 1
Abstract
Background
Glutathione is a potential therapy for systemic lupus erythematosus, but its role in allergic rhinitis (AR) has not been determined. This report probed into the actions of glutathione in AR, so as to supplement evidence for a therapeutical countermeasure for AR.
Methods
In this study, peripheral blood mononuclear cells (PBMCs) of patients were extracted and processed with glutathione. PBMCs and nasal mucosa tissues were collected from AR mouse models treated with or without glutathione. The proportions of Th17/Treg cell markers and autophagy-related molecules in the nasal mucosa, PBMCs or Th17/Treg cells were assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB) or flow cytometry analysis, and serum contents of related factors were analyzed by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was applied to observe the thickness of mouse mucosa.
Results
IL-17A, RORγt, Beclin1 and LC3-II/LC3-I levels were increased in AR patients, while Foxp3 and P62 were decreased. The serum contents of IL-17A and eosinophil cationic protein (ECP) in AR patients were elevated, but IL-10 level was reduced. In PBMCs of AR patients, the levels of IL-17A and LC3-II were increased, and the levels of Foxp3 and P62 were decreased, while these changes could be reversed by glutathione. In AR mouse models, glutathione could balance Th17/Treg cells, reduce autophagy, correct the levels of related cytokines in mouse serum, and shrunk mucosa thickness.
Conclusion
Glutathione could rescue the imbalance of Treg/Th17 cells by suppressing intracellular autophagy, which might be beneficial to the treatment of AR patients.
中文翻译:
谷胱甘肽通过抑制细胞内自噬对变应性鼻炎患者treg/Th17细胞平衡的调节作用
摘要
背景
谷胱甘肽是治疗系统性红斑狼疮的潜在疗法,但其在过敏性鼻炎 (AR) 中的作用尚未确定。本报告探讨了谷胱甘肽在 AR 中的作用,为 AR 的治疗对策补充证据。
方法
在这项研究中,提取患者的外周血单个核细胞 (PBMC) 并用谷胱甘肽进行处理。从用或不用谷胱甘肽处理的 AR 小鼠模型中收集 PBMC 和鼻粘膜组织。通过定量实时聚合酶链反应 (qRT-PCR)、蛋白质印迹 (WB) 或流式细胞术分析评估鼻粘膜、PBMC 或 Th17/Treg 细胞中 Th17/Treg 细胞标志物和自噬相关分子的比例,酶联免疫吸附试验(ELISA)分析血清相关因子含量。应用苏木精-伊红(HE)染色观察小鼠黏膜厚度。
结果
AR 患者的 IL-17A、RORγt、Beclin1 和 LC3-II/LC3-I 水平升高,而 Foxp3 和 P62 水平降低。AR患者血清IL-17A和嗜酸性粒细胞阳离子蛋白(ECP)含量升高,但IL-10水平降低。AR 患者 PBMC 中 IL-17A 和 LC3-II 水平升高,Foxp3 和 P62 水平降低,而这些变化可以被谷胱甘肽逆转。在 AR 小鼠模型中,谷胱甘肽可以平衡 Th17/Treg 细胞,减少自噬,纠正小鼠血清中相关细胞因子的水平,并收缩粘膜厚度。
结论
谷胱甘肽可以通过抑制细胞内自噬来挽救 Treg/Th17 细胞的失衡,这可能有利于 AR 患者的治疗。