ArticleThe Journal of clinical investigation2016
Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 2 of them syntheses that pooled it.
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Who cites it
115 citing papers in PubMed, 2 syntheses or guidelines pooled it, 198 citations in OpenAlex.
- Outcome and clinical features in juvenile myasthenia gravis: A systematic review and meta-analysis.Frontiers in neurology · 2023Pooled it
- Sex steroids and autoimmune rheumatic diseases: state of the art.Nature reviews. Rheumatology · 2020Pooled it
- High-Dose Neonatal Vitamin A Supplementation Transiently Decreases Thymic Function in Early Infancy.The Journal of nutrition · 2020Trial
- Role of sex and gender in autoimmune thyroid diseases: mechanisms and knowledge gaps.Reviews in endocrine & metabolic disorders · 2026Review
- Sex-dependent mechanisms in rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- Thymic selection of the T cell receptor repertoire is biased toward autoimmunity in females.eLife · 2026Article
- Association of Demographic, Clinical, and Environmental Factors With Disease Severity in Adult Myasthenia Gravis: A Multicenter Cross-Sectional Study.CNS neuroscience & therapeutics · 2026Article
- Sex matters: mechanistic insights into sex-driven patterns of autoimmunity and implications for pharmacotherapy.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Association between sex-hormone binding globulin and cardiovascular events in patients with rheumatoid arthritis.Clinical rheumatology · 2026Article
- Sex Differences in the Impact of Obesity on Immunity.Immunological reviews · 2026Review
- Genetic insights into biological aging and myasthenia gravis: a Mendelian randomization study of telomere length, epigenetic clocks, and mitochondrial DNA copy number.Clinical epigenetics · 2026Article
- Age-related thymic involution: Mechanistic insights and rejuvenating approaches to restore immune function.Science advances · 2026Review
- Review
- The multisystem impact of perimenopausal hormonal fluctuations on chronic disease risk.Frontiers in endocrinology · 2026Review
- Thymic CT attenuation score in SAPHO syndrome: a comparative study with rheumatoid arthritis, ankylosing spondylitis, and healthy controls.Frontiers in immunology · 2026Article
- Sex differences in immune cells: mechanistic perspectives and clinical correlates in physiology and disease.Frontiers in immunology · 2026Review
- Sex as a modifier of genetic risk for type 1 diabetes.Diabetes, obesity & metabolism · 2025Review
- The sex-biased chromatin modifier SMC1A promotes autoimmunity by shaping inflammatory pathways in patients with SLE.Nature communications · 2025Article
- Immunological Targets in Generalized Myasthenia Gravis Treatment: Where Are We Going Now?Brain sciences · 2025Review
- Sex Bias in Autoimmunity: New Findings and New Opportunities.JID innovations : skin science from molecules to population health · 2025Review
55 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autoimmune diseases affect 5% to 8% of the population, and females are more susceptible to these diseases than males. Here, we analyzed human thymic transcriptome and revealed sex-associated differences in the expression of tissue-specific antigens that are controlled by the autoimmune regulator (AIRE), a key factor in central tolerance. We hypothesized that the level of AIRE is linked to sexual dimorphism susceptibility to autoimmune diseases. In human and mouse thymus, females expressed less AIRE (mRNA and protein) than males after puberty. These results were confirmed in purified murine thymic epithelial cells (TECs). We also demonstrated that AIRE expression is related to sexual hormones, as male castration decreased AIRE thymic expression and estrogen receptor α-deficient mice did not show a sex disparity for AIRE expression. Moreover, estrogen treatment resulted in downregulation of AIRE expression in cultured human TECs, human thymic tissue grafted to immunodeficient mice, and murine fetal thymus organ cultures. AIRE levels in human thymus grafted in immunodeficient mice depended upon the sex of the recipient. Estrogen also upregulated the number of methylated CpG sites in the AIRE promoter. Together, our results indicate that in females, estrogen induces epigenetic changes in the AIRE gene, leading to reduced AIRE expression under a threshold that increases female susceptibility to autoimmune diseases.
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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.