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. 2021 Apr;18(2):388-397.
doi: 10.1007/s10388-020-00773-2. Epub 2020 Sep 13.

Key molecules involved in the Th17/Treg balance are associated with the pathogenesis of reflux esophagitis and Barrett's esophagus

Juan Liu  1   2 , Yao Luo  3 , Jun Wang  1 , Chunhui Xi  1 , Yu Chen  1 , Guodong Yang  1 , Ying Ling  4
Affiliations

Key molecules involved in the Th17/Treg balance are associated with the pathogenesis of reflux esophagitis and Barrett's esophagus

Juan Liu et al. Esophagus. 2021 Apr.

Abstract

Background: Reflux esophagitis (RE) impairs the squamous epithelium that normally lines the esophagus, and contributes to the replacement of the damaged squamous lining by the intestinal metaplasia of Barrett's esophagus (BE), which is considered as a precursor of esophageal adenocarcinoma. This study aimed to investigate the changes in the balance of Th17/Treg and the related key molecules in the pathogenesis of RE and BE and evaluate the diagnostic and predictive value of the molecules in patients with these diseases.

Methods: The proportions of Th17 and Treg in RE and BE patients were estimated using flow cytometric analysis. Key molecules involving in the Th17/Treg balance, including RORγt, Foxp3, IL-17, IL-6, IL-10, and TGF-β, were measured using quantitative real-time PCR (qRT-PCR) and ELISA analyses. The diagnostic and predictive value of the Th17/Treg ratio and its key regulators was evaluated using a receiver operating characteristic assay (ROC). In addition, the Spearman correlation analysis explored the relationship between the Th17/Treg ratio and the clinical characteristics.

Results: An increased ratio of Th17/Treg was observed in RE and BE compared with the normal controls, and the proportion of Th17/Treg in BE was further increased compared with RE patients. Moreover, the expression levels of RORγt, IL-17, IL-6, and TGF-β were elevated, while the levels of Foxp3 and IL-10 were reduced in patients when compared to the controls. Compared with the RE groups, the levels of IL-17 were significantly higher in BE patients, while the Foxp3 levels were significant decreased. In addition, the Th17/Treg ratio also showed high diagnostic significance and considerable predictive value for the clinical outcomes in patients with RE and BE.

Conclusion: The balance of Th17/Treg was impaired in patients with RE and BE. Th17/Treg may be involved in the development of both RE and BE through regulating the release of inflammatory cytokines, but the concrete mechanisms maybe different in the two diseases. The imbalance of Th17/Treg ratio and the related key molecules had a certain clinical diagnosis and prediction potential for RE and BE.

Keywords: Barrett’s esophagus; Diagnosis; Prognosis; Reflux esophagitis; Th17/Treg balance.

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