Circulating microRNA Expression Profiling Identifies miR-125a-5p Promoting T Helper 1 Cells Response in the Pathogenesis of Hashimoto's Thyroiditis

Abstract

MicroRNAs (miRNAs) have emerged as key regulators of cellular processes by suppressing target mRNAs at the posttranscriptional level. However, little is known regarding the expression of miRNAs in peripheral blood mononuclear cells (PBMCs) from Hashimoto's thyroiditis (HT) patients. Therefore, 38 HT patients and 36 healthy volunteers were enrolled in this study to identify HT-mediated changes in miRNA expression. Over 1,000 dysregulated miRNAs and their biological functions in the HT patients were identified. Among them, miR-125a-5p expression was upregulated and inversely correlated with low levels of MAF, a transcription factor that inhibits Th1 cells activity and the production of IFN-γ. Luciferase assay results demonstrated that MAF is a direct target gene of miR-125a-5p. Moreover, the proportion of circulating Th1 cells and the transcript levels of IFN-γ were increased in the HT patients. MiR-125a-5p expression positively correlated with the proportion of circulating Th1 cells and the serum concentrations of anti-thyroperoxidase antibodies in the HT patients. Interestingly, knockdown of miR-125a-5p in CD4 + T cells resulted in an elevated level of MAF but decreased the proportion of Th1 cells and the transcript level of IFN-γ in vitro. Furthermore, upregulated miR-125a-5p and IFN-γ transcript levels and downregulated MAF expression were detected in thyroid tissues from HT patients. Receiver operating characteristic (ROC) curves suggested that miR-125a-5p has a crucial role in the HT. Our results demonstrate that the elevated levels of miR-125a-5p contribute to the Th1 cells response in the HT patients and may be involved in the pathogenesis of HT.

Elevated Expression of the Long Noncoding RNA MAFTRR in Patients with Hashimoto’s Thyroiditis

“…Th1 cells are the predominant lymphocytes in the thyroid tissues from the HT patients which directly destroy thyroid follicular cells by activating cytotoxic lymphocytes and macrophages [7]. The previous studies have indicated that the proportion of peripheral Th1 cells was significantly increased in patients with HT [4,21]. Therefore, the factors contributing to Th1 cells in HT deserve further investigation.…”

“…It was first described in Japan by Dr. Hakaru Hashimoto over a century ago [2]. The clinical features of HT patients are characterized by increased thyroid volume, lymphocyte infiltration of interstitium between thyroid follicles, and the presence of specific antibodies to thyroid antigens, including antithyroglobulin antibody (TgAb) and antithyroperoxidase antibody (TPOAb) [3,4]. HT was long considered a rare disease until the change in diagnostic modality, mostly, the introduction of thyroid function and thyroid antibodies tests [5].…”

“…Maf was a Th2-associated transcription factor, which was poorly expressed in Th1 cells and decreased the production of interferon γ (IFN-γ) [16]. Studies focused on immune cells have indicated that Th1 cells play an important role in HT [4,17], but the molecular mechanisms causing Th1 cells imbalance remain unknown. The relationship between MAFTRR and Th1 cells inspired us to hypothesize that MAFTRR may play a crucial pathogenic role in the development of HT.…”

Circular RNA circNUP214 Modulates the T Helper 17 Cell Response in Patients With Rheumatoid Arthritis

“…Human peripheral blood mononuclear cells (PBMCs) were isolated by density-gradient centrifugation over Ficoll-Hypaque solution (Haoyang Biological Technology Co., Tianjin, China) and stored at -80°C for quantitative real-time polymerase chain reaction (qRT–PCR). Human CD4 + T cells were isolated from PBMCs using human CD4 microbeads (Miltenyi Biotec GmbH, Bergisch Gladbach, Germany) as previously described ( 33 ). Human PBMCs and CD4 + T cells were cultured with RPMI-1640 medium (Gibco, California, USA) containing 10% foetal bovine serum (Gibco) for transfection.…”

Comprehensive Analysis of lncRNA Expression Profile and the Potential Role of ENST00000604491 in Graves’ Disease

“…cDNA reverse transcription and quantitative real-time PCR (qRT–PCR) were performed as previously described [ 18 ]. The primers are summarized in Supplemental Table S2 .…”