ArticleEndocrinology2009
Studies in mice deficient for the autoimmune regulator (Aire) and transgenic for the thyrotropin receptor reveal a role for Aire in tolerance for thyroid autoantigens.
Article in Endocrinology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Myasthenia gravis and five autoimmune diseases: a bidirectional Mendelian randomization study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Pooled it
- Altered expression of autoimmune regulator in infant down syndrome thymus, a possible contributor to an autoimmune phenotype.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Exploring antigenic variation in autoimmune endocrinopathy.Frontiers in immunology · 2025Review
- Review
- Effects of exogenous melatonin on clinical and pathological features of a human thyroglobulin-induced experimental autoimmune thyroiditis mouse model.Scientific reports · 2019Article
- Glycosylation in the Thyroid Gland: Vital Aspects of Glycoprotein Function in Thyrocyte Physiology and Thyroid Disorders.International journal of molecular sciences · 2018Review
- Genetic immunization with mouse thyrotrophin hormone receptor plasmid breaks self-tolerance for a murine model of autoimmune thyroid disease and Graves' orbitopathy.Clinical and experimental immunology · 2018Article
- Twenty Years of AIRE.Frontiers in immunology · 2018Review
- High-level intrathymic thyrotrophin receptor expression in thyroiditis-prone mice protects against the spontaneous generation of pathogenic thyrotrophin receptor autoantibodies.Clinical and experimental immunology · 2017Article
- Genes Outside the Major Histocompatibility Complex Locus Are Linked to the Development of Thyroid Autoantibodies and Thyroiditis in NOD.H2h4 Mice.Endocrinology · 2017Article
- Critical Differences between Induced and Spontaneous Mouse Models of Graves' Disease with Implications for Antigen-Specific Immunotherapy in Humans.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases.The Journal of clinical investigation · 2016Article
- Breaking tolerance to thyroid antigens: changing concepts in thyroid autoimmunity.Endocrine reviews · 2014Review
- Role of self-tolerance and chronic stimulation in the long-term persistence of adenovirus-induced thyrotropin receptor antibodies in wild-type and transgenic mice.Thyroid : official journal of the American Thyroid Association · 2012Article
- Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity.Lipids in health and disease · 2012Article
- Article
- Review and hypothesis: does Graves' disease develop in non-human great apes?Thyroid : official journal of the American Thyroid Association · 2011Review
- An attempt to induce "Graves' disease of the gonads" by immunizing mice with the luteinizing hormone receptor provides insight into breaking tolerance to self-antigens.Thyroid : official journal of the American Thyroid Association · 2011Article
- Thyroid antigens, not central tolerance, control responses to immunization in BALB/c versus C57BL/6 mice.Thyroid : official journal of the American Thyroid Association · 2009Article
- Autoimmune thyroiditis: a model uniquely suited to probe regulatory T cell function.Journal of autoimmunityReview
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The autoimmune regulator (Aire) mediates central tolerance for many autoantigens, and autoimmunity occurs spontaneously in Aire-deficient humans and mice. Using a mouse model of Graves' disease, we investigated the role of Aire in tolerance to the TSH receptor (TSHR) in Aire-deficient and wild-type mice (hyperthyroid-susceptible BALB/c background). Mice were immunized three times with TSHR A-subunit expressing adenovirus. The lack of Aire did not influence T-cell responses to TSHR protein or TSHR peptides. However, antibody levels were higher in Aire-deficient than wild-type mice after the second (but not the third) immunization. After the third immunization, hyperthyroidism persisted in a higher proportion of Aire-deficient than wild-type mice. Aire-deficient mice were crossed with transgenic strains expressing high or low-intrathyroidal levels of human TSHR A subunits. In the low-expressor transgenics, Aire deficiency had the same effect on the pattern of the TSHR antibody response to immunization as in nontransgenics, although the amplitude of the response was lower in the transgenics. High-expressor A-subunit transgenics were unresponsive to immunization. We examined intrathymic expression of murine TSHR, thyroglobulin, and thyroid peroxidase (TPO), the latter two being the dominant autoantigens in Hashimoto's thyroiditis (particularly TPO). Expression of the TSHR and thyroglobulin were reduced in the absence of Aire. Dramatically, thymic expression of TPO was nearly abolished. In contrast, the human A-subunit transgene, lacking a potential Aire-binding motif, was unaffected. Our findings provide insight into how varying intrathymic autoantigen expression may modulate thyroid autoimmunity and suggest that Aire deficiency may contribute more to developing Hashimoto's thyroiditis than Graves' disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.