T-cell exhaustion-related genes in Graves' disease: a comprehensive genome mapping analysis.

Background: T-cell exhaustion (Tex) can be beneficial in autoimmune diseases, but its role in Graves' disease (GD), an autoimmune disorder of the thyroid, remains unknown. This study investigated Tex-related gene expression in GD patients to discern the potential contributions of these genes to GD pathogenesis and immune regulation.

Methods: Through gene landscape analysis, a protein-protein interaction network of 40 Tex-related genes was constructed.

PTPN22 through the regulation of Th17/Treg balance acts as a potential target for the treatment of Graves' disease.

Graves' disease (GD) is an autoimmune disease and the most common cause of hyperthyroidism. While the phosphotyrosine phosphatase non-receptor type 22 (PTPN22) variant is associated with GD susceptibility, its precise role and mechanism in GD remain unclear. To investigate this, we induced GD in mice using Ad-TSHR289 and isolated CD4+ T cells from spleen tissues.

Circular RNA circPHF16 enhances IL-17A expression and secretion by sequestering miR-378a-3p to activate the IL6ST axis in Graves' disease.

Interleukin-17A (IL-17A) plays a pivotal role in the pathogenesis of Graves' disease (GD), an autoimmune disorder affecting thyroid function, but the detailed regulatory mechanisms remain elusive. Circular RNAs (circRNAs) have emerged as key regulators of IL-17A expression and secretion in autoimmune diseases, yet their specific role in GD, especially within CD4 + T lymphocytes, are not well understood. In this study, a circRNA, circPHF16 (hsa_circ_0090364) was found to be highly expressed in the peripheral blood mononuclear cells and serum of GD patients.

TSHR-based chimeric antigen receptor T cell specifically deplete auto-reactive B lymphocytes for treatment of autoimmune thyroid disease.

Graves' disease (GD) is a prominent antibody-mediated autoimmune disorder characterized by stimulating antibodies (TRAb) that target the thyroid-stimulating hormone receptor (TSHR). Targeting and eliminating TRAb-producing B lymphocytes hold substantial therapeutic potential for GD. In this study, we engineered a novel chimeric antigen receptor T cell (CAR-T) therapy termed TSHR-CAR-T.

Circular RNA HIPK3 contributes to hyperglycemia and insulin homeostasis by sponging miR-192-5p and upregulating transcription factor forkhead box O1.

It has been shown that circular RNAs, a class of non-coding RNA molecules, play an important role in the regulation of glucose and lipid homeostasis. In the present study, we sought to investigate the function of circular RNA HIPK3 (circHIPK3) in diabetes-associated metabolic disorders, including hyperglycemia and insulin resistance. Results show that oleate stimulated circHIPK3 increase, and that circHIPK3 enhanced the stimulatory effect of oleate on adipose deposition, triglyceride (TG) content, and cellular glucose content in HepG2 cells.

Optimal iodine supplementation during antithyroid drug therapy for Graves' disease is associated with lower recurrence rates than iodine restriction.

Objective: A relationship between iodine intake and the effectiveness of antithyroid drug (ATD) therapy for Graves' disease (GD) has been suggested, and strict restriction of iodine intake has been tried in the treatment of GD in some studies. However, it is unclear whether dietary iodine supplementation improves the prognosis of ATD therapy for GD. This study aimed to clarify whether optimal iodine supplementation during antithyroid drug therapy for GD is associated with lower recurrence rates than iodine restriction.

Iodinated TG in Thyroid Follicles Regulate TSH/TSHR Signaling for NIS Expression.

Our previous research has suggested that high degree of iodinated thyroglobulin (TG) may inhibit the expression and function of sodium iodide symporter (NIS), but the underlying mechanism remains unclear. In present study, we discuss a newly constructed follicle model in vitro, which was used to simulate the follicular structure of the thyroid and explore the regulatory roles of iodinated TG in the follicular lumen on NIS expression. The results showed that both NIS expression and PKA activity were increased in lowly iodinated TG group, while decreased NIS expression with increased PKC activity was found in highly iodinated TG group.

Iodinated TG in Thyroid Follicular Lumen Regulates TTF-1 and PAX8 Expression via TSH/TSHR Signaling Pathway.

Our previous study showed that highly iodinated thyroglobulin (TG) inhibited thyroid transcription factor-1 (TTF-1) and paired box gene 8 (PAX8) expression, but the potential mechanism remains unclear. In this study, we constructed a thyroid follicle model in vitro to mimic its natural physiological structure and explored how iodinated TG in the follicular lumen tuned TTF-1 and PAX8 expression. Our data showed that lowly iodinated TG enhanced PKA activity while upregulation of both TTF-1 and PAX8 expression; and that highly iodinated TG triggered PKC activity while suppression of TTF-1 and PAX8 expression.

Low Iodine in the Follicular Lumen Caused by Cytoplasm Mis-localization of Sodium Iodide Symporter may Induce Nodular Goiter.

Iodine is a key ingredient in the synthesis of thyroid hormones and also a major factor in the regulation of thyroid function. A local reduction of iodine content in follicular lumen leads to overexpression of local thyroid-stimulating hormone receptor (TSHr), which in turn excessively stimulates the regional thyroid tissue, and result in the formation of nodular goiter. In this study, we investigated the relationship between iodine content and sodium iodide symporter (NIS) expression by using the clinical specimens from patients with nodular goiter and explored the pathogenesis triggered by iodine deficiency in nodular goiter.

Glycolysis-associated enzymes existing in the follicular lumen of the thyroid may interfere with energy metabolism.

Synthesis and storage of the thyroid hormone precursor, thyroglobulin (TG), occurs within the follicular lumen of the thyroid and the TG is then absorbed into cells for further processing before release into the blood. However, the mechanism of energy metabolism in the follicular lumen of the thyroid remains unknown. In the present study, the three dimensional structure of thyroid follicles was constructed using a primary culture of swine cells and the follicular protein was identified via matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

Upregulation of TSHR, TTF-1, and PAX8 in Nodular Goiter Is Associated with Iodine Deficiency in the Follicular Lumen.

Objective. It has been testified that iodine regulates thyroid function by controlling thyroid-restricted genes expression and is closely related to diffuse goiter and thyroid dysfunction. However, the effects of follicular lumen iodine, the main form of iodine reserve in the body, on thyroid-restricted genes in nodular goiter are poorly understood.

Presence of free triiodothyronine and free thyroxine in thyroid follicles may be correlated with the quick secretion of thyroid hormones under certain physiological conditions.

Thyroid cells are polarized and the follicle structure, consisting of follicle epithelial cells, is a prerequisite for thyroid hormone synthesis. However, a reliable in vitro model simulating thyroid function is not currently available. To the best of our knowledge, the present study reports for the first time a simulated follicle by inoculation of human thyroid cells on the filter in a Transwell plate to maintain the polarity of thyroid cells.