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OVA 持续激发变应性鼻炎小鼠模型中 TGF-β1+Breg 细胞与辅助性 T 细胞亚群的变化。

Changes among TGF-β1 Breg cells and helper T cell subsets in a murine model of allergic rhinitis with prolonged OVA challenge.

机构信息

Department of Otolaryngology of Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, China.

Department of Otolaryngology of Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, China.

出版信息

Int Immunopharmacol. 2019 Apr;69:347-357. doi: 10.1016/j.intimp.2019.01.009. Epub 2019 Feb 15.

DOI:10.1016/j.intimp.2019.01.009
PMID:30776643
Abstract

BACKGROUND

Allergic rhinitis is a common allergic disease resulting from inappropriate Th2 cell-mediated immune responses to environmental antigens. As such, regulatory B cells and T helper cells play a critical role in the occurrence and development of allergic rhinitis.

METHODS

Wild-type mice received ovalbumin (OVA) intranasal challenge for varied lengths of time, then the inflammatory state of their nasal mucosa was analyzed by histology. Changes to the proportion and function of TGF-β1 Bregs, T helper cells and plasma cells was analyzed by flow cytometry, real-time PCR, ELISA and cytometric bead arrays. Finally, changes in expression of upstream transcription factors related to helper T cells and STAT proteins were detected by western blot.

RESULTS

The most severe inflammatory response was observed in the mucosal tissue, where the percentage of TGF-β1 Bregs and Tregs decreased, and the percentage and function of Th2 and plasma cells increased significantly. With prolonged OVA challenge, the proportion of TGF-β1 Bregs and Tregs increased. These factors regulated Th2 cell polarization state and gradually restored balance of the inflammatory state in the nasal mucosa. Moreover, changes to upstream transcription factors and STAT proteins were found to be positively correlated with changes to helper T cells.

CONCLUSION

TGF-β1 Bregs cooperated with Treg cells in the development of allergic rhinitis and its recovery process. Reconstitution of nasal mucosal immunity was facilitated via regulation of the proportion and function of helper T cells.

摘要

背景

过敏性鼻炎是一种常见的过敏性疾病,由环境抗原引起的 Th2 细胞介导的免疫反应不当引起。因此,调节性 B 细胞和辅助性 T 细胞在过敏性鼻炎的发生和发展中起着关键作用。

方法

野生型小鼠接受卵清蛋白(OVA)鼻内挑战不同时间,然后通过组织学分析其鼻黏膜的炎症状态。通过流式细胞术、实时 PCR、ELISA 和细胞计数珠阵列分析 TGF-β1 Bregs、辅助性 T 细胞和浆细胞的比例和功能变化。最后,通过 Western blot 检测与辅助性 T 细胞和 STAT 蛋白相关的上游转录因子的表达变化。

结果

在黏膜组织中观察到最严重的炎症反应,其中 TGF-β1 Bregs 和 Tregs 的比例下降,Th2 和浆细胞的比例和功能显著增加。随着 OVA 挑战时间的延长,TGF-β1 Bregs 和 Tregs 的比例增加。这些因素调节了 Th2 细胞的极化状态,并逐渐恢复了鼻黏膜炎症状态的平衡。此外,发现上游转录因子和 STAT 蛋白的变化与辅助性 T 细胞的变化呈正相关。

结论

TGF-β1 Bregs 与 Treg 细胞在过敏性鼻炎的发展及其恢复过程中协同作用。通过调节辅助性 T 细胞的比例和功能,促进了鼻黏膜免疫的重建。

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