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Th17/Treg 比值改变作为特发性膜性肾病发病机制的一种可能机制。

Altered Th17/Treg ratio as a possible mechanism in pathogenesis of idiopathic membranous nephropathy.

作者信息

Motavalli Roza, Etemadi Jalal, Soltani-Zangbar Mohammad Sadegh, Ardalan Mohamad-Reza, Kahroba Houman, Roshangar Leila, Nouri Mohammad, Aghebati-Maleki Leili, Khiavi Farhad Motavalli, Abediazar Sima, Mehdizadeh Amir, Hojjat-Farsangi Mohammad, Mahmoodpoor Ata, Kafil Hossein Samadi, Zolfaghari Mohamadali, Ahmadian Heris Javad, Yousefi Mehdi

机构信息

Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Kidney Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Cytokine. 2021 May;141:155452. doi: 10.1016/j.cyto.2021.155452. Epub 2021 Feb 8.

Abstract

Idiopathic membranous nephropathy (IMN) as a single organ autoimmune disease is a main cause of nephrotic syndrome in adults which is determined through autoantibodies to podocytes proteins. Th17/regulatory T (Treg) balance has emerged as a prominent factor in the regulation of autoimmunity. In this study, we evaluated the balance of Th17 and Treg cells, expression level of related master transcription factors, cytokines and microRNAs in mononuclear cells of peripheral blood of 30 patients with IMN and 30 healthy individuals before treatment. No significant variation was observed in Th17 cell frequency, retinoic acid receptor-related orphan nuclear receptor γt (RORɣt), signal transducer and Activator of transcription 3(STAT3), IL-17, and IL-23, while IL-21, IL-4, and IL-10 had significant increase in mRNA expression and protein level of peripheral blood mononuclear cells in IMN cases. Reduction in the percentage of Treg cells was also accompanied with significantly decreased expression of Forkhead box P3(FOXP3) and Transforming growth factor beta(TGF-β) in IMN patients compared to the control group. Our study revealed that Th17 cells themselves might not be engaged in the pathogenesis of newly diagnosed patients with IMN; however, decreased T reg cells and increased ratio of Th17/Treg lymphocytes might display a role in the pathogenesis of IMN before treatment.

摘要

特发性膜性肾病(IMN)作为一种单一器官自身免疫性疾病,是成人肾病综合征的主要病因,其由针对足细胞蛋白的自身抗体所决定。Th17/调节性T(Treg)平衡已成为自身免疫调节中的一个突出因素。在本研究中,我们评估了30例IMN患者和30例健康个体治疗前外周血单个核细胞中Th17和Treg细胞的平衡、相关主转录因子、细胞因子和微小RNA的表达水平。在Th17细胞频率、维甲酸受体相关孤儿核受体γt(RORɣt)、信号转导和转录激活因子3(STAT3)、白细胞介素-17(IL-17)和白细胞介素-23方面未观察到显著差异,而在IMN患者外周血单个核细胞中,白细胞介素-21(IL-21)、白细胞介素-4(IL-4)和白细胞介素-10(IL-10)的mRNA表达和蛋白水平显著增加。与对照组相比,IMN患者中Treg细胞百分比的降低还伴随着叉头框P3(FOXP3)和转化生长因子β(TGF-β)表达的显著下降。我们的研究表明,Th17细胞本身可能不参与新诊断IMN患者的发病机制;然而,Treg细胞减少和Th17/Treg淋巴细胞比例增加可能在治疗前IMN的发病机制中发挥作用。

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