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谷胱甘肽通过抑制细胞内自噬对过敏性鼻炎患者调节性 T 细胞/Th17 细胞平衡的调控作用。

Regulatory effect of glutathione on treg/Th17 cell balance in allergic rhinitis patients through inhibiting intracellular autophagy.

机构信息

Department of Otolaryngology Head & Neck Surgery, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Nursing, Wuxi Taihu University, Wuxi, Jiangsu, China.

出版信息

Immunopharmacol Immunotoxicol. 2021 Feb;43(1):58-67. doi: 10.1080/08923973.2020.1850762. Epub 2020 Dec 7.

DOI:10.1080/08923973.2020.1850762
PMID:33285073
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.

摘要

背景

谷胱甘肽可能是治疗系统性红斑狼疮的一种方法,但它在过敏性鼻炎(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 的治疗对策提供补充证据。

方法

本研究从接受谷胱甘肽处理或未处理的 AR 小鼠模型的外周血单个核细胞(PBMC)和鼻黏膜组织中提取和处理患者的 PBMC。通过实时定量聚合酶链反应(qRT-PCR)、Western blot(WB)或流式细胞术分析评估鼻黏膜、PBMC 或 Th17/Treg 细胞中 Th17/Treg 细胞标志物和自噬相关分子的比例,通过酶联免疫吸附试验(ELISA)分析相关因子的血清含量。通过苏木精-伊红(HE)染色观察小鼠黏膜的厚度。

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 患者的血清 IL-17A 和嗜酸性粒细胞阳离子蛋白(ECP)含量升高,而 IL-10 水平降低。在 AR 患者的 PBMC 中,IL-17A 和 LC3-II 水平升高,Foxp3 和 P62 水平降低,而谷胱甘肽可以逆转这些变化。在 AR 小鼠模型中,谷胱甘肽可以通过抑制细胞内自噬来平衡 Th17/Treg 细胞,减少自噬,纠正小鼠血清中相关细胞因子的水平,并缩小黏膜厚度。

结论

谷胱甘肽通过抑制细胞内自噬来纠正 Treg/Th17 细胞失衡,这可能有益于 AR 患者的治疗。

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