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ABSTRACT: Context
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.Objective
To investigate how certain miRNA causes aberrant CD4+ T cell function in GD patients.Methods
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.Results
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.Conclusion
The increased expression of miR-4443 induced CD4+ T cells dysfunction by targeting TRAF4, which may cause GD.
SUBMITTER: Qi Y
PROVIDER: S-EPMC5671953 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature

Qi Yicheng Y Zhou Yulin Y Chen Xinxin X Ye Lei L Zhang Qianwei Q Huang Fengjiao F Cui Bin B Lin Dongping D Ning Guang G Wang Weiqing W Wang Shu S
Frontiers in immunology 20171101
<h4>Context</h4>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.<h4>Objective</h4>To investigate how certain miRNA causes aberrant CD4+ T cell function in GD patients.<h4>Methods</h4>We compared the expression pattern of miRNAs in CD4+ T cells from untreated GD (UG ...[more]