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• W2766881582 abstract "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." @default.
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• W2766881582 date "2017-11-01" @default.
• W2766881582 modified "2023-10-14" @default.
• W2766881582 title "MicroRNA-4443 Causes CD4+ T Cells Dysfunction by Targeting TNFR-Associated Factor 4 in Graves’ Disease" @default.
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• W2766881582 doi "https://doi.org/10.3389/fimmu.2017.01440" @default.
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