Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
J Cell Physiol. 2021 Apr;236(4):2829-2839. doi: 10.1002/jcp.30047. Epub 2020 Sep 14.
In the course of the coronavirus disease 2019 (COVID-19), raising and reducing the function of Th17 and Treg cells, respectively, elicit hyperinflammation and disease progression. The current study aimed to evaluate the responses of Th17 and Treg cells in COVID-19 patients compared with the control group. Forty COVID-19 intensive care unit (ICU) patients were compared with 40 healthy controls. The frequency of cells, gene expression of related factors, as well as the secretion levels of cytokines, were measured by flow cytometry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay techniques, respectively. The findings revealed a significant increase in the number of Th17 cells, the expression levels of related factors (RAR-related orphan receptor gamma [RORγt], IL-17, and IL-23), and the secretion levels of IL-17 and IL-23 cytokines in COVID-19 patients compared with controls. In contrast, patients had a remarkable reduction in the frequency of Treg cells, the expression levels of correlated factors (Forkhead box protein P3 [FoxP3], transforming growth factor-β [TGF-β], and IL-10), and cytokine secretion levels (TGF-β and IL-10). The ratio of Th17/Treg cells, RORγt/FoxP3, and IL-17/IL-10 had a considerable enhancement in patients compared with the controls and also in dead patients compared with the improved cases. The findings showed that enhanced responses of Th17 cells and decreased responses of Treg cells in 2019-n-CoV patients compared with controls had a strong relationship with hyperinflammation, lung damage, and disease pathogenesis. Also, the high ratio of Th17/Treg cells and their associated factors in COVID-19-dead patients compared with improved cases indicates the critical role of inflammation in the mortality of patients.
在 2019 年冠状病毒病（COVID-19）过程中，分别升高和降低 Th17 和 Treg 细胞的功能会引起过度炎症和疾病进展。本研究旨在评估 COVID-19 患者与对照组相比 Th17 和 Treg 细胞的反应。将 40 例 COVID-19 重症监护病房（ICU）患者与 40 名健康对照进行比较。通过流式细胞术、实时聚合酶链反应和酶联免疫吸附测定技术分别测量细胞频率、相关因子的基因表达以及细胞因子的分泌水平。研究结果显示，与对照组相比，COVID-19 患者 Th17 细胞数量、相关因子（维甲酸相关孤儿受体γ[RORγt]、白细胞介素 17[IL-17]和白细胞介素 23[IL-23]）的表达水平以及白细胞介素 17 和白细胞介素 23 细胞因子的分泌水平均显著升高。相反，患者 Treg 细胞的频率、相关因子（叉头框蛋白 P3[FoxP3]、转化生长因子-β[TGF-β]和白细胞介素 10[IL-10]）的表达水平以及细胞因子（TGF-β 和 IL-10）的分泌水平显著降低。与对照组相比，患者的 Th17/Treg 细胞、RORγt/FoxP3 和 IL-17/IL-10 比值明显升高，死亡患者与改善患者相比也明显升高。研究结果表明，与对照组相比，2019-n-CoV 患者 Th17 细胞反应增强和 Treg 细胞反应减弱与过度炎症、肺损伤和疾病发病机制密切相关。此外，COVID-19 死亡患者与改善患者相比，Th17/Treg 细胞及其相关因子的高比值表明炎症在患者死亡率中的关键作用。
