MicroRNA-4443 Causes CD4+ T Cells Dysfunction by Targeting TNFR-Associated Factor 4 in Graves' Disease.
MicroRNA-4443 Causes CD4+ T Cells Dysfunction by Targeting TNFR-Associated Factor 4 in Graves' Disease.
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MicroRNA-4443 通过靶向格雷夫斯病中 TNFR 相关因子 4 导致 CD4 T 细胞功能障碍
DOI：
10.3389/fimmu.2017.01440
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发表时间：
2017
影响因子：
7.3
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Qi Y;Zhou Y;Chen X;Ye L;Zhang Q;Huang F;Cui B;Lin D;Ning G;Wang W;Wang S
CD4+ T 细胞功能异常在格雷夫斯病 (GD) 的发病过程中起着至关重要的作用。 MicroRNA (miRNA) 是 T 细胞激活、增殖和细胞因子产生的重要调节因子。然而，miRNA 对 GD 中 CD4+ T 细胞功能障碍的影响仍不清楚。研究某些 miRNA 如何导致 GD 患者 CD4+ T 细胞功能异常。我们比较了未经治疗的 GD (UGD) 患者和健康对照者 CD4+ T 细胞中 miRNA 的表达模式。选择最显着失调的 miRNA，并分析它们与临床参数的相关性。评估了 miR-4443 对 CD4+ T 细胞细胞因子产生和增殖的影响。潜在的基因靶标已被识别和验证。与健康受试者相比，GD 患者的 CD4+ T 细胞中的 miRNA 表达谱具有独特的模式。 miR-10a、miR-125b 和 miR-4443 是三种最显着失调的 miRNA。在 UGD 患者的独立数据集中，升高的 miR-4443 水平与临床参数密切相关 (N = 40)，而 miR-4443 在甲状腺功能正常且 TRAb 水平阴性的 GD 患者中正常表达。我们发现 miR-4443 直接抑制 TNFR 相关因子 (TRAF) 4 的表达，从而增加 CD4+ T 细胞细胞因子的分泌以及通过 NF-κB 途径的增殖。此外，GD患者中TRAF4水平与miR-4443呈负相关，敲低TRAF4与miR-4443过表达具有相似的效果。 miR-4443表达增加通过靶向TRAF4诱导CD4+T细胞功能障碍，这可能导致GD。
Aberrant CD4+ T cell function plays a critical role in the process of Graves’ disease (GD). MicroRNAs (miRNAs) are important regulators of T cell activation, proliferation, and cytokine production. However, the contribution of miRNAs to CD4+ T cell dysfunction in GD remains unclear. To investigate how certain miRNA causes aberrant CD4+ T cell function in GD patients. We compared the expression pattern of miRNAs in CD4+ T cells from untreated GD (UGD) patients with those from healthy controls. The most significantly dysregulated miRNAs were selected and their correlations with clinical parameters were analyzed. The effect of miR-4443 on CD4+ T cells cytokines production and proliferation was assessed. The potential gene target was identified and validated. GD patients had unique pattern of miRNA expression profile in CD4+ T cells comparing to healthy subjects. miR-10a, miR-125b, and miR-4443 were the three most significantly dysregulated miRNAs. The elevated miR-4443 levels were strongly correlated with clinical parameters in an independent dataset of UGD patients (N = 40), while miR-4443 was normally expressed in GD patients with euthyroidism and negative TRAb level. We found that miR-4443 directly inhibited TNFR-associated factor (TRAF) 4 expression to increase CD4+ T cells cytokines secretion as well as proliferation through the NF-κB pathway. Furthermore, the TRAF4 levels in GD patients were inversely correlated with miR-4443, and knocking down TRAF4 had a similar effect with miR-4443 overexpression. The increased expression of miR-4443 induced CD4+ T cells dysfunction by targeting TRAF4, which may cause GD.
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影响因子：
4.1
作者：
Meira M;Sievers C;Hoffmann F;Rasenack M;Kuhle J;Derfuss T;Kappos L;Lindberg RL
通讯作者：
Lindberg RL
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影响因子：
3.7
作者：
Li X;Qi Y;Ma X;Huang F;Guo H;Jiang X;Hong J;Lin D;Cui B;Ning G;Xu L;Wang S
通讯作者：
Wang S
影响因子：
3.7
作者：
Qi, Yicheng;Li, Xiaoli;Wang, Shu
通讯作者：
Wang, Shu
影响因子：
5.8
作者：
Antonelli, A;Rotondi, M;Serio, M
通讯作者：
Serio, M
影响因子：
5.8
作者：
Aniszewski, JP;Valyasevi, RW;Bahn, RS
通讯作者：
Bahn, RS