Th17 and regulatory lymphocyte subsets such as Tregs and Bregs have been reported to play important roles in autoimmune diseases. The aim of this work was to perform quantitative studies of circulating Th17, Tregs, and Bregs in patients with new-onset Graves’ disease (GD). Twenty GD patients and 20 healthy controls were involved in this study. Blood samples were taken for flow cytometry detection of CD4⁺IL-17⁺ Th17, CD4⁺Foxp3⁺ Tregs, and CD19⁺CD1d^hiCD5⁺ Bregs and meanwhile, for real-time PCR measurement of gene expressions of RORγt, IL-17 and IL-10. The proportions of Tregs and Bregs as well as the Foxp3 gene expression but not IL-10 were significantly decreased in GD group compared with the healthy controls. The frequency of Th17 together with the gene expressions of RORγt and IL-17 were significantly increased in the GD group. Furthermore, the Th17/Treg ratio was also significantly higher in GD group. A significant positive correlation between Th17 and TSAb (r=0.656, p<0.001) but significant negative correlations between Treg/Breg and TSAb (r=-0.339, p=0.032; r=-0.759, p<0.001) were identified among the participants. This study indicated that increased Th17 and impaired Treg responses, along with a decreased number of CD19⁺CD1d^hiCD5⁺ Breg cells, were involved in GD pathogenesis.

Objective This study explored whether circulating exosomes effectively participate in the inflammatory response in Hashimoto thyroiditis (HT). Design Exosomes were extracted from the serum of 30 patients with HT and 30 healthy control (HC) subjects. The expression of thyroperoxidase (TPO), thyroglobulin, high mobility group box 1 (HMGB1), heat shock protein 60 (HSP60), major histocompatibility complex class II (MHC-II), and intercellular adhesion molecule 1 (ICAM1) in exosomes was determined by Western blotting. Flow cytometry and immunofluorescence were performed to confirm that exosomes were taken up by healthy peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs). Then, either DCs or PBMCs were stimulated with HT exosomes (serum exosomes from patients with HT) or HC exosomes (serum exosomes from HC subjects) in the presence or absence of Toll-like receptor (TLR)2/3 inhibitors. Results TPO, HSP60, and MHC-II expression was higher in HT exosomes than in HC exosomes. Exosomes were mainly taken up by CD14+ monocytes and CD11c+ DCs. After DCs were stimulated by HT exosomes, significant elevations were observed in MyD88, TRIF, and p-P65 expression; median fluorescence intensity of CD40 and CD83; and IL-6 production. After stimulating PBMCs with HT exosomes, CD11c+TLR2+/TLR3+ and CD4+IFN-γ+Th1/IL-17A+Th17A cell percentages were significantly elevated, and CD4+CD25+Foxp3+ Treg cell percentage was significantly decreased. HT exosomes induced increased IL-17A and IFN-γ production, whereas IL-10 production was suppressed. However, addition of TLR2 or TLR3 inhibitor reversed most of the abovementioned results. Conclusions Our study demonstrates that HT exosomes can present antigens to DCs and bind TLR2/3, causing DC activation via the nuclear factor κB signaling pathway, leading to an imbalance in CD4+ T lymphocyte differentiation, and potentially contributing to HT onset.

Purpose: The aim of the present prospective follow-up study was to explore the early indicators of hypothyroidism and final changes in thyroid volume in subacute thyroiditis (SAT) patients. Methods: We enrolled 61 SAT patients and followed them for 2 years to assess the incidence of hypothyroidism and changes in thyroid volume. Binary logistic regression and receiver operating characteristic (ROC) curves were used for data analysis. Results: During the 2-year follow-up period, we found that the volume of the thyroid gland in SAT patients at 1 and 2 years was significantly smaller than that in the healthy control group, which was significantly smaller compared to the initial thyroid volume after SAT onset (p<0.001). Also the thyroid volume of SAT patients with hypothyroidism was significantly smaller than that of SAT patients without hypothyroidism. The early maximum thyroid stimulating hormone (TSH) value (within 3 months after SAT onset) was closely related to the incidence of hypothyroidism at 2 years. The OR value was 1.18 (95% CI 1.01-1.38, P=0.032). The early maximum TSH value had a maximum area under the ROC curve (AUC) of 0.866 for the development of hypothyroidism 2 years after SAT onset vs. euthyroidism (P<0.001). Conclusions: The thyroid volume of patients increased significantly after the onset of SAT, while during the follow-up the thyroid volume decreased and the thyroid volume at 1 and 2 years was significantly smaller than that of normal healthy subjects, especially in SAT patients with hypothyroidism. Furthermore, the early maximum TSH value could be used as effective indicators of the development of hypothyroidism 2 years after the onset of SAT.

Hashimoto's thyroiditis (HT) is a common autoimmune disease accompanied by lymphocyte infiltration and thyroid tissue destruction. IL-34 was first described in 2008, and its involvement in the development of many autoimmune diseases has been recently identified. However, whether IL-34 is a regulatory factor in HT is unclear. Here, we demonstrate that IL-34 is expressed on thyroid follicular epithelial cells and that IL-34 expression is significantly reduced in thyroid tissue in patients with HT and spontaneous autoimmune thyroiditis (SAT) models. Serum IL-34 levels in patients with HT are also significantly reduced. In addition, IL-34 is associated with thyroid autoantibodies in both thyroid tissue and serum. Furthermore, our data show that IL-34 participates in the apoptosis resistance of thyrocytes in HT induced by CSF-1R and may be a potential indicator for evaluating thyrocyte damage.