Hashimoto thyroiditis (HT) is a prototypic organ-specific autoimmune thyroid disease, for which the exact etiology remains unclear. The aim of this study was to investigate dynamic changes in regulatory T cell (Treg) and T helper 17 cell (Th17) populations in patients with HT at different stages of thyroid dysfunction, as well as to analyze the possible correlation between the Treg/Th17 cell axis and autoimmune status in HT. We assessed thyroid function and autoantibody serology both in HT patients and in healthy controls (HCs) and divided HT patients into three subgroups according to thyroid function. We then determined the percentages of Treg and Th17 cells in peripheral blood mononuclear cells and analyzed mRNA expression of the Treg and Th17 cell-defining transcription factors Foxp3 and RORγt. In addition, serum levels of TGF-β and IL-17A were assessed. We found that the percentage of Treg cells, Foxp3 mRNA levels, and the ratio of Treg/Th17 cells were all significantly lower in HT patients, while Th17 cell percentages and RORγt mRNA levels were significantly higher. Interestingly, we also observed significant differences in these measurements between HT patient subgroups. Serum IL-17A levels were markedly increased in HT patients, while serum concentrations of TGF-β were lower, compared to HCs. The ratio of Treg/Th17 cells was negatively correlated with the levels of serum thyroperoxidase antibody, thyroglobulin antibody, and thyrotropin (TSH) in HT patients. Taken together, our data suggest that the balance between Treg and Th17 cells shifts in favor of Th17 cells during clinical progression of HT, which is negatively correlated with levels of thyroid-specific autoantibodies and TSH, implying that Treg/Th17 cell imbalance may contribute to thyroid damage in HT.
Purpose. To explore the possible role of MIF and Th17 cells in the thyroid-specific autoimmune damage of Hashimoto's thyroiditis (HT). Material and Methods. We enrolled 40 HT patients and 30 healthy controls and divided HT patients into euthyroid subset (n = 22) and subclinical or overt hypothyroidism subset (n = 18). The percentages of Th17 cells and expressions of MIF, interleukin 17A (IL-17A) mRNA in PBMCs, as well as serum concentrations of MIF, and IL-17A, and thyroid functions, and thyroid-specific autoantibodies (TPOAb, TgAb) were detected by flow cytometry, real-time RT-PCR, ELISA, and ECLIA in all subjects. Results. MIF mRNA, IL-17A mRNA expressions and Th17 cells percentages, serum MIF, and IL-17A protein levels were all significantly higher in HT patients, even in euthyroid subgroup. Additionally, the differences became more obvious in dysfunction subgroup. Importantly, both MIF levels and Th17 cells percentage were positively correlated with serum TPOAb, TgAb, and thyrotropin (TSH) levels in HT patients. Conclusions. These data suggest that MIF and Th17 cells increased dynamically and positively correlated with the markers of thyroid autoimmune damage, which indicated that interaction between MIF and Th17 cells may participate in the pathogenesis and development of thyroid-specific autoimmunity in HT.
Some certain genetic polymorphisms have been considered to implicate in the pathogenesis and progression of autoimmune diseases and may predispose to an early stage of general autoimmune susceptibility. Recent studies have been conducted to investigate the association between macrophage migration inhibitory factor- (MIF-) 173G/C gene polymorphism and autoimmune diseases; however, the results were not exactly identical. In the present study, a systematic review and meta-analysis of case-control studies was performed to estimate the relationship. A comprehensive search of PubMed, Ebsco, EMbase, WanFang databases and CNKI was done. Odds ratio (ORs) and corresponding 95% confidence intervals (CIs) were combined to pool the effect size. The publication bias was examined by Begg’s funnel plots and Egger’s test. RevMan 5.3 and STATA 12.0 software were used for statistical processing. 23 papers were included, and the results revealed that MIF-173G/C was significantly associated with an increased risk of autoimmune diseases in five genetic models (recessive genetic model: OR=1.95, 95% CI: 1.52-2.50; dominant genetic model: OR=1.35, 95% CI: 1.24-1.46; allele model: OR=1.32, 95% CI: 1.23-1.41; homozygote model: OR=1.92, 95% CI: 1.57-2.35; heterozygote model: OR=4.92, 95% CI: 4.03-6.02), whether in Asia, Europe, or North America. Furthermore, subgroup analysis showed an increasing risk in rheumatoid arthritis (RA), ulcerative colitis (UC), Crohn’s disease (CD), atopic dermatitis (AD), Henoch-Schonlein purpura (HSP), and Henoch-Schonlein purpura nephritis (HSPN), but it was not related to the susceptibility of autoimmune hepatitis (AIH). Therefore, it could be considered that MIF-173G/C polymorphism could increase the susceptibility of autoimmune diseases, while there may be the discrepancy of disease entity.
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