ArticleThe Journal of experimental medicine2021
Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE autoregulation.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Systematic and proactive evaluation of AIRE missense variant effects.American journal of human genetics · 2026Article
- Long-term follow-up of autoimmune polyendocrine syndrome type 1 in Norway.The Journal of clinical endocrinology and metabolism · 2026Article
- Limited penetrance of dominantly inherited AIRE variants in a population-based cohort.Human molecular genetics · 2026Article
- SCID newborn screening: seven-year performance and outcomes including T-cell lymphopenia in Catalonia (Spain).Frontiers in immunology · 2026Article
- AIRE transcriptional condensates in central tolerance: a multiscale mechanistic perspective.Frontiers in immunology · 2026Review
- Aire-dependent interferon signalling shapes thymocyte maturation and central tolerance in mice.Communications biology · 2025Article
- Systematic and proactive evaluation of AIRE missense variant effects.bioRxiv : the preprint server for biology · 2025Article
- A novel heterozygous pathogenicJournal of human immunity · 2025Article
- Article
- UTAP2: an enhanced user-friendly transcriptome and epigenome analysis pipeline.BMC bioinformatics · 2025Article
- Aire Mutations and Autoimmune Diseases.Advances in experimental medicine and biology · 2025Review
- The CRISPR-Cas9 System Is Used to Edit the Autoimmune Regulator Gene in Vitro and in Vivo.Advances in experimental medicine and biology · 2025Article
- High-resolution transcriptional impact of AIRE: effects of pathogenic variants p.Arg257Ter, p.Cys311Tyr, and polygenic risk variant p.Arg471Cys.Frontiers in immunology · 2025Article
- Mechanism for controlled assembly of transcriptional condensates by Aire.Nature immunology · 2024Article
- Primary and secondary defects of the thymus.Immunological reviews · 2024Review
- Human autoantibodies neutralizing type I IFNs: From 1981 to 2023.Immunological reviews · 2024Review
- Insm1 regulates mTEC development and immune tolerance.Cellular & molecular immunology · 2023Article
- A partial form of AIRE deficiency underlies a mild form of autoimmune polyendocrine syndrome type 1.The Journal of clinical investigation · 2023Article
- Thymic mimetic cells function beyond self-tolerance.Nature · 2023Article
- Dominant-negative heterozygous mutations in AIRE confer diverse autoimmune phenotypes.iScience · 2023Article
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Authors and funding
25 authors at 5 institutions in 5 countries.
Funding
Abstract
The autoimmune regulator (AIRE) is essential for the establishment of central tolerance and prevention of autoimmunity. Interestingly, different AIRE mutations cause autoimmunity in either recessive or dominant-negative manners. Using engineered mouse models, we establish that some monoallelic mutants, including C311Y and C446G, cause breakdown of central tolerance. By using RNAseq, ATACseq, ChIPseq, and protein analyses, we dissect the underlying mechanisms for their dominancy. Specifically, we show that recessive mutations result in a lack of AIRE protein expression, while the dominant mutations in both PHD domains augment the expression of dysfunctional AIRE with altered capacity to bind chromatin and induce gene expression. Finally, we demonstrate that enhanced AIRE expression is partially due to increased chromatin accessibility of the AIRE proximal enhancer, which serves as a docking site for AIRE binding. Therefore, our data not only elucidate why some AIRE mutations are recessive while others dominant, but also identify an autoregulatory mechanism by which AIRE negatively modulates its own expression.
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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.