Graves'-like hyperthyroidism is induced by immunizing BALB/c mice with adenovirus expressing the thyrotropin receptor (TSHR) or its A-subunit. Nonantigen-specific immune strategies can block disease development and some reduce established hyperthyroidism, but these approaches may have unforeseen side effects. Without immune stimulation, antigens targeted to the mannose receptor induce tolerance.
View Article and Find Full Text PDFContext: In Graves' disease, thyroid-stimulating antibodies (TSAb) activate the TSH receptor (TSHR) causing hyperthyroidism. Serum polyclonal TSAb are difficult to study because of their extremely low serum levels.
Objective: Our objective was to determine whether monoclonal TSAb possess characteristics previously reported for polyclonal autoantibodies in Graves' sera.
TSH receptor (TSHR) antibodies and hyperthyroidism are induced by immunizing mice with adenovirus encoding the TSHR or its A-subunit. Depleting regulatory T cells (Treg) exacerbates thyrotoxicosis in susceptible BALB/c mice and induces hyperthyroidism in normally resistant C57BL/6 mice. Vitamin D plays an important role in immunity; high dietary vitamin D intake suppresses (and low intake enhances) adaptive immune responses.
View Article and Find Full Text PDFPurpose: To evaluate how irradiation affects thyroid autoimmunity in mouse models of Hashimoto's thyroiditis and Graves' hyperthyroidism.
Materials And Methods: Non-obese diabetic (NOD)-H2(h4) mice spontaneously develop anti-thyroglobulin (Tg) antibodies and thyroiditis when supplied with sodium iodine (NaI) in the drinking water. BALB/c mice develop anti-thyrotropin receptor (TSHR) antibodies and hyperthyroidism following immunization with adenovirus expressing TSHR (Ad-TSHR).
The glycoprotein hormone receptor hinge region connects the leucine-rich and transmembrane domains. The prevalent concept is that the hinge does not play a significant role in ligand binding and signal transduction. Portions of the hinge are redundant and can be deleted by mutagenesis or are absent in certain species.
View Article and Find Full Text PDFHyperthyroidism in Graves' disease is caused by thyroid-stimulating autoantibodies to the TSH receptor (TSHR), whereas hypothyroidism in Hashimoto's thyroiditis is associated with thyroid peroxidase and thyroglobulin autoantibodies. In some Graves' patients, thyroiditis becomes sufficiently extensive to cure the hyperthyroidism with resultant hypothyroidism. Factors determining the balance between these two diseases, the commonest organ-specific autoimmune diseases affecting humans, are unknown.
View Article and Find Full Text PDFIn addition to the biochemical inhibition of thyroid hormone synthesis, antithyroid drugs including methimazole (MMI) may have immunosuppressive effect through inhibition of major histocompatibility complex (MHC) class I and II expressions on non-professional (thyrocytes) and professional (macrophages and B cells) antigen presenting cells (APCs). Dendritic cells (DCs) are another professional APCs and very likely play the most important role in the primary immune response. Therefore, we focused in this study on evaluating the effect of MMI on DC function in mice.
View Article and Find Full Text PDFStimulating the immune system by in vivo expression of the thyrotropin receptor (TSHR) is an efficient means to induce Graves' disease experimentally. For example, BALB/c mice injected with dendritic cells (DCs) infected with adenovirus encoding the full-length TSHR (AdTSHR) develop hyperthyroidism, albeit at a low incidence (36%). Recent observations suggest that the shed TSHR A-subunit, rather than the full-length receptor, is the autoantigen responsible for initiating/enhancing immune responses leading to thyroid stimulating antibodies (TSAb) and hyperthyroidism.
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