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SARS-CoV2 感染通过改变 SOCS1 水平诱导 miR-155 表达和偏向性 Th17/Treg 平衡:一项临床研究。

SARS-CoV2 infection induce miR-155 expression and skewed Th17/Treg balance by changing SOCS1 level: A clinical study.

机构信息

Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Behbahan Faculty of Medical Sciences, Behbahan, Iran.

出版信息

Cytokine. 2023 Sep;169:156248. doi: 10.1016/j.cyto.2023.156248. Epub 2023 Jun 8.

DOI:10.1016/j.cyto.2023.156248
PMID:37307689
原文链接:
https://pmc.ncbi.nlm.nih.gov/articles/PMC10247889/
Abstract

BACKGROUND

One of the regulators in severe acute respiratory syndrome coronavirus2 (SARS-CoV2) infection is miRNAs. In COVID-19 patients, immunological responses to SARS-CoV2 infection may be impacted by miR-155, a miRNA associated to inflammation.

MATERIALS AND METHODS

Peripheral blood mononuclear cells (PBMCs) of 50 confirmed COVID-19 patients /Healthy Controls (HCs) was isolated by Ficoll. The frequency of T helper 17 and regulatory T cells was analyzed by flowcytometry. The RNA was extracted from each sample and after synthesis of c-DNA, the relative expression of miR-155, suppressor of cytokine signaling (SOCS-1), Signal transducer and activator of transcription 3(STAT3), and Fork Head Box Protein 3 (FoxP3) was evaluated by real-time PCR. The protein level of STAT3, FoxP3 and RORγT in the isolated PBMCs measured by western blotting. The serum level of IL-10, TGF-β, IL-17 and IL21 was assessed by ELISA method.

RESULTS

The population of Th17 cells showed a significant rise, whereas Treg cells reduced in COVID-19 cases. The master transcription factor of Treg (FoxP3) and Th17 (RORγT) relative expression showed the same pattern as flowcytometry. STAT3 level of expression at RNA and protein level increased in COVID-19 cases. FOXP3 and SOCS-1 proteins were down-regulated. The relative expression of miR-155, up-regulated in PBMC of COVID-19 patients and revealed a negative correlation with SOCS-1. The serum cytokine profile showed a reduction in TGF-β, on the other hand an increase was seen in IL-17, IL-21 and IL-10 in COVID-19 cases toward control group.

CONCLUSION

Based on the studies conducted in this field, it can be suggested that Th17/Treg in covid-19 patients can be affected by miR-155 and it can be considered a valuable diagnostic and prognostic factor in this disease.

摘要

背景

严重急性呼吸综合征冠状病毒 2 (SARS-CoV2) 感染的调控因子之一是 microRNAs。在 COVID-19 患者中,对 SARS-CoV2 感染的免疫反应可能受 microRNA-155 的影响,microRNA-155 与炎症有关。

材料和方法

通过 Ficoll 分离 50 例确诊 COVID-19 患者/健康对照 (HCs) 的外周血单核细胞 (PBMCs)。通过流式细胞术分析辅助性 T 细胞 17 和调节性 T 细胞的频率。从每个样本中提取 RNA,合成 cDNA 后,通过实时 PCR 评估 microRNA-155、细胞因子信号转导抑制因子 (SOCS-1)、信号转导和转录激活因子 3 (STAT3) 和叉头框蛋白 3 (FoxP3) 的相对表达。通过 Western blot 测量分离的 PBMC 中 STAT3、FoxP3 和 RORγT 的蛋白水平。通过 ELISA 法评估血清中白细胞介素 10 (IL-10)、转化生长因子-β (TGF-β)、白细胞介素 17 (IL-17) 和白细胞介素 21 (IL-21) 的水平。

结果

Th17 细胞群体显著增加,而 COVID-19 病例中的 Treg 细胞减少。Treg (FoxP3) 和 Th17 (RORγT) 的主转录因子相对表达呈现出与流式细胞术相同的模式。COVID-19 病例中 STAT3 表达水平的 RNA 和蛋白水平均升高。FOXP3 和 SOCS-1 蛋白下调。COVID-19 患者 PBMC 中 miR-155 的相对表达上调,并与 SOCS-1 呈负相关。血清细胞因子谱显示 TGF-β减少,另一方面 COVID-19 病例中 IL-17、IL-21 和 IL-10 增加。

结论

基于该领域的研究,可以认为 Th17/Treg 在 COVID-19 患者中可能受到 miR-155 的影响,因此可以作为该疾病有价值的诊断和预后因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab7/10247889/3c18bd0393f6/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab7/10247889/2ea2f4ef73bc/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab7/10247889/a81e664fee96/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab7/10247889/d3084bab8944/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab7/10247889/14d436bec491/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab7/10247889/3c18bd0393f6/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab7/10247889/2ea2f4ef73bc/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab7/10247889/a81e664fee96/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab7/10247889/d3084bab8944/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab7/10247889/14d436bec491/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab7/10247889/3c18bd0393f6/gr5_lrg.jpg

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