Search

Background: Recent clinical studies have demonstrated the suppressive effect of selenium (Se) treatment on serum thyroid-specific antibody titers in patients with autoimmune thyroiditis (AIT), but the mechanism underlying this process is not clear. The aim of the present study was to investigate the effects of selenium on the incidence and severity of AIT, titers of thyroid autoantibodies, and selenoprotein expression in thyroid in a spontaneous autoimmune thyroiditis (SAT) model. Methods: NOD.H-2h4 mice at four weeks of age were randomly divided into control, iodine supplement (SAT), and selenium supplement groups (SAT+Se). Mice were given 0.005% sodium iodide water for eight weeks to induce SAT and then 0.3 mg/L sodium selenite in drinking water for 8 weeks and 16 weeks. The severity of lymphocytic infiltration in the thyroid, serum thyroglobulin antibody (TgAb) titers, serum selenium concentration, expression of glutathione peroxidase-1 (GPx1), thioredoxin reductase-1 (Txnrd1), and peroxiredoxin 5 were measured. Results: Serum selenium concentration significantly increased after selenium supplementation. Serum TgAb levels were significantly lower in the selenium group compared with the SAT group ( p<0.05). The prevalence of thyroiditis and the degree of infiltration of lymphocytes decreased gradually over time in the group provided with selenium supplementation. The expression of GPx1 and Txnrd1 by Western blotting were found to be significantly higher in the SAT+Se group than in other groups ( p<0.05). Conclusions: These results indicate that selenium treatment can increase the function of antioxidation by upregulating the expression of selenoproteins in the thyroid and have an inhibitory effect on TgAb titers, which may have an impact on AIT. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are a class of critical epigenetic regulators involved in several autoimmune diseases. Our previous study reported an miR-326-induced increase in T helper (Th) 17 cells in a mouse model of Hashimoto's thyroiditis (HT), but the pathogenic effect of miR-326 in HT patients has not been verified. The goal of the present study was to explore the pathogenic role of miR-326 and its underlying molecular mechanism in HT patients. Methods: A total of 58 HT patients and 55 normal controls were enrolled in this study. We examined whether Th17 cells and miR-326 were aberrantly altered in the peripheral blood mononuclear cells (PBMCs) of HT patients with flow cytometry and real-time polymerase chain reaction. Levels of membrane interleukin (IL)-23R (mIL-23R) were determined by flow cytometry and Western blot to explore the critical role of mIL-23R in the development of Th17 cells. Isolated CD3+ T cells were used to further investigate the ectodomain shedding of mIL-23R by a disintegrin and metalloprotease (ADAM17). Furthermore, miR-326 inhibitor and mimics were transfected into PBMCs derived from HT patients and healthy controls to verify the regulation of ADAM17 by miR-326. Results: We observed elevated miR-326 levels in the PBMCs of HT patients compared with those in the PBMCs of healthy controls. Consistent with IL-23-induced STAT3 overactivation, substantially more HT patient-derived PBMCs differentiated into Th17 cells under polarization culture conditions, which may, at least in part, have resulted from enhanced mIL-23R levels. Furthermore, ADAM17, an ectodomain sheddase of mIL-23R, was targeted and negatively regulated by miR-326. Inhibiting ADAM17 might attenuate the ectodomain shedding of mIL-23R. Conclusions: Our findings suggest that the effect of miR-326 on the IL-23/IL-23R/Th17 cell axis in HT patients might be partially due to the targeting of ADAM17. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that sphingosine-1-phosphate (S1P), a pleiotropic bioactive sphingolipid metabolite synthesized intracellularly by two closely related sphingosine kinases (SphKs), SphK1 and SphK2, is involved in inflammation. However, the role of SphKs/S1P/S1P receptors (S1PRs) in autoimmune thyroiditis (AIT) has not been studied to date. Methods: This study examined whether SphK1/S1P/S1PR1 signaling is aberrantly altered in thyroid tissues and serum of both AIT patients and a spontaneously autoimmune thyroiditis (SAT) mouse model. Murine CD4+T cells were employed to further investigate the downstream signaling of SphK1/S1P/S1PR1. Furthermore, a total of 102 NOD.H-2h4 mice, randomly divided into different groups, were used to investigate the therapeutic effect of S1PR1 blockade and its potential mechanism. Results: We found that components of the SphK1/S1P/S1PR1 pathway were abnormally expressed in patients with Hashimoto thyroiditis and in a SAT mouse model. In addition, S1P could activate signal transducer and activator of transcription 3 (STAT3) through S1PR1 and its downstream signaling pathways in CD4+T cells of NOD.H-2h4 mice. Furthermore, an in vivo study demonstrated that blocking S1PR1 by FTY720 administration could reduce the incidence and severity of thyroiditis and goiter in SAT mice in a time-dependent manner. The proportions of STAT3-related and inflammation-related cell subtypes, such as T helper 1, T helper 17, and follicular T helper cells, were elevated in the SAT group when compared to the control group, and these cell subtypes decreased after FTY720 administration. Furthermore, the downstream inflammatory cytokines of STAT3 were also downregulated after FTY720 administration. Conclusion: The present study shows that blocking Sphk1/S1P/S1PR1 signaling can ameliorate the severity of AIT, providing evidence of a promising therapeutic target for AIT. [ABSTRACT FROM AUTHOR]

Exosomes have been intensively studied in autoimmune diseases, and circulating exosomes and microvesicles have also been explored in autoimmune thyroiditis (AITD). However, the role of thyroid cell-derived exosomes in immune responses is unclear. We showed that IFN-γ-treated Nthy-ori 3-1 cell-derived exosomes (IFN-γ-Exo) harbored TPO, HSP60 and MHC-II and activated dendritic cells (DCs) in vitro. Compared with Exo-targeted DCs (DC Exo), IFN-γ-Exo-targeted DCs (DC IFN-γ-Exo) promoted the expression and release of proinflammatory cytokines, such as IFN-γ, IL-17A and IL-22, from CD4+ T lymphocytes and inhibited the expression and release of anti-inflammatory cytokines, such as IL-4, IL-10 and TGF-β1; however, IFN-γ-Exo did not have this effect compared with Nthy-ori 3-1 cell-derived exosomes (Exo). DC IFN-γ-Exo stimulates the expression and release of cytokines from CD4+ T lymphocytes more efficiently than IFN-γ-Exo. Thus, DC IFN-γ-Exo may effectively induce CD4+ T lymphocyte-mediated immune responses and play a role in the occurrence and development of AITD. • IFN-γ-treated thyroid cell-derived exosomes (IFN-γ-Exo) express TPO, HSP60, MHC-II. • IFN-γ-Exo activate dendritic cells (DCs). • IFN-γ-Exo need to activate DCs before triggering CD4+ T lymphocyte differentiation. [ABSTRACT FROM AUTHOR]

Background: Resistance to thyroid hormone beta (RTHβ) results in symptoms of both increased and decreased thyroid hormone action. The effect of thyroid hormone changes in different types of autoimmune thyroid disease (AITD) in RTHβ is dynamic.Case Presentation: A 25-year-old Asian female had a RTHβ Y321C mutation with Hashimoto's thyroiditis and type 2 diabetes mellitus. She was followed-up through gestation and two years postpartum, revealing development of postpartum thyroiditis (PPT) with characteristic wide fluctuations in serum thyrotropin levels, and of spontaneous recovery from an episode of transient hypothyroidism. The presence of RTHβ did not prolong thyroiditis duration nor progressed toward permanent hypothyroidism. Prenatal genetic analysis was not performed on the unaffected fetus, and did not result in congenital hypothyroidism, possibly because maternal free thyroxine (FT4) levels were mildly elevated at less than 50% above the reference range in early gestation and gradually decreased to less than 20% after the 28th gestational week.Conclusion: In RTHβ patients with autoimmune thyroid disease, episodes of thyroid dysfunction can significantly alter thyrotropin levels. During pregnancy, mildly elevated maternal free thyroxine levels less than 20% above the upper limit may not be harmful to unaffected fetuses. Unnecessary thyroid hormone control and fetal genetic testing was avoided during the gestational period with monthly follow-up. [ABSTRACT FROM AUTHOR]

Background: Iodine is an essential component of thyroid hormones; either low or high intake may lead to thyroid disease. We observed an increase in the prevalence of overt hypothyroidism, subclinical hypothyroidism, and autoimmune thyroiditis with increasing iodine intake in China in cohorts from three regions with different levels of iodine intake: mildly deficient (median urinary iodine excretion, 84 μg per liter), more than adequate (median, 243 μg per liter), and excessive (median, 651 μg per liter). Participants enrolled in a baseline study in 1999, and during the five-year follow-up through 2004, we examined the effect of regional differences in iodine intake on the incidence of thyroid disease. Methods: Of the 3761 unselected subjects who were enrolled at baseline, 3018 (80.2 percent) participated in this follow-up study. Levels of thyroid hormones and thyroid autoantibodies in serum, and iodine in urine, were measured and B-mode ultrasonography of the thyroid was performed at baseline and follow-up. Results: Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the cumulative incidence of overt hypothyroidism was 0.2 percent, 0.5 percent, and 0.3 percent, respectively; that of subclinical hypothyroidism, 0.2 percent, 2.6 percent, and 2.9 percent, respectively; and that of autoimmune thyroiditis, 0.2 percent, 1.0 percent, and 1.3 percent, respectively. Among subjects with euthyroidism and antithyroid antibodies at baseline, the five-year incidence of elevated serum thyrotropin levels was greater among those with more than adequate or excessive iodine intake than among those with mildly deficient iodine intake. A baseline serum thyrotropin level of 1.0 to 1.9 mIU per liter was associated with the lowest subsequent incidence of abnormal thyroid function. Conclusions: More than adequate or excessive iodine intake may lead to hypothyroidism and autoimmune thyroiditis. N Engl J Med 2006;354:2783-93. [ABSTRACT FROM AUTHOR]