ArticleThe Journal of experimental medicine2004
Gene dosage--limiting role of Aire in thymic expression, clonal deletion, and organ-specific autoimmunity.
Article in The Journal of experimental medicine, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 290 citations in OpenAlex.
- Review
- Aire-dependent interferon signalling shapes thymocyte maturation and central tolerance in mice.Communications biology · 2025Article
- Impaired Aire-dependent IFN signaling in the thymus precedes the protective autoantibodies to IFNα.The Journal of experimental medicine · 2025Article
- Deconstructing the Thymic Microenvironment Through Genesis to Senescence.Immunological reviews · 2025Review
- The Autoimmune Regulator (AIRE) Gene, The Master Activator of Self-Antigen Expression in the Thymus.Advances in experimental medicine and biology · 2025Review
- Aire Mutations and Autoimmune Diseases.Advances in experimental medicine and biology · 2025Review
- Single cell characterization of blood and expanded regulatory T cells in autoimmune polyendocrine syndrome type 1.iScience · 2024Article
- Analysis of theInternational journal of molecular sciences · 2024Article
- A partial form of AIRE deficiency underlies a mild form of autoimmune polyendocrine syndrome type 1.The Journal of clinical investigation · 2023Article
- Characterisation of APS-1 Experimental Models Is Crucial for Development of Novel Therapies.BioMed research international · 2023Article
- Disruption of thymic central tolerance by infection with murine roseolovirus induces autoimmune gastritis.The Journal of experimental medicine · 2022Article
- AIRE in context: Leveraging chromatin plasticity to trigger ectopic gene expression.Immunological reviews · 2022Review
- Autoimmunity and Cancer-Two Sides of the Same Coin.Frontiers in immunology · 2022Review
- The NOD Mouse Beyond Autoimmune Diabetes.Frontiers in immunology · 2022Review
- AIRE deficiency, from preclinical models to human APECED disease.Disease models & mechanisms · 2021Review
- Thymus and autoimmunity.Seminars in immunopathology · 2021Review
- Age-Related Changes in Thymic Central Tolerance.Frontiers in immunology · 2021Review
- Review
- AAV9-mediated AIRE gene delivery clears circulating antibodies and tissue T-cell infiltration in a mouse model of autoimmune polyglandular syndrome type-1.Clinical & translational immunology · 2020Article
- The Role of the Thymus in the Immune Response.Thoracic surgery clinics · 2019Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inactivation of the autoimmune regulator (Aire) gene causes a rare recessive disorder, autoimmune polyendocrine syndrome 1 (APS1), but it is not known if Aire-dependent tolerance mechanisms are susceptible to the quantitative genetic changes thought to underlie more common autoimmune diseases. In mice with a targeted mutation, complete loss of Aire abolished expression of an insulin promoter transgene in thymic epithelium, but had no effect in pancreatic islets or the testes. Loss of one copy of Aire diminished thymic expression of the endogenous insulin gene and the transgene, resulting in a 300% increase in islet-reactive CD4 T cells escaping thymic deletion in T cell receptor transgenic mice, and dramatically increased progression to diabetes. Thymic deletion induced by antigen under control of the thyroglobulin promoter was abolished in Aire homozygotes and less efficient in heterozygotes, providing an explanation for thyroid autoimmunity in APS1. In contrast, Aire deficiency had no effect on thymic deletion to antigen controlled by a systemic H-2K promoter. The sensitivity of Aire-dependent thymic deletion to small reductions in function makes this pathway a prime candidate for more subtle autoimmune quantitative trait loci, and suggests that methods to increase Aire activity would be a potent strategy to lower the incidence of organ-specific autoimmunity.
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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.