ArticleThe Journal of clinical investigation2016
LYN- and AIRE-mediated tolerance checkpoint defects synergize to trigger organ-specific autoimmunity.
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 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
21 citing papers in PubMed, 23 citations in OpenAlex.
- Immune checkpoints in a genetically engineered mouse model of spontaneous autoimmune uveitis.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
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- KDM3B Predicts Expression Signature, Prognosis Value, and Immune Characteristics of Cancers: A Pan-Cancer Analysis.BioMed research international · 2026Article
- Spontaneous organ-specific eye autoimmune disease resulting from two engineered gene mutations compromising immune tolerance.Frontiers in immunology · 2026Review
- Thymic Mimetic Cells: Ontogeny as Immunology.Annual review of cell and developmental biology · 2024Review
- Tracking the role of Aire in immune tolerance to the eye with a TCR transgenic mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Ikaros is a principal regulator of AireScience immunology · 2023Article
- CTLA-4 on thymic epithelial cells complements Aire for T cell central tolerance.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Immune Privilege Furnishes a Niche for Latent Infection.Frontiers in ophthalmology · 2022Review
- Article
- Microbiota and Ocular Diseases.Frontiers in cellular and infection microbiology · 2021Review
- Comparative Analysis of Global Proteome and Lysine Acetylome Between Naive CD4Frontiers in immunology · 2021Article
- Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy.Frontiers in pediatrics · 2021Review
- An AIREless Breath: Pneumonitis Caused by Impaired Central Immune Tolerance.Frontiers in immunology · 2020Review
- Non-receptor tyrosine kinase signaling in autoimmunity and therapeutic implications.Pharmacology & therapeutics · 2019Review
- Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance.Science translational medicine · 2019Article
- Autoimmune Regulator is required in female mice for optimal embryonic development and implantation†.Biology of reproduction · 2019Article
- Lessons from primary immunodeficiencies: Autoimmune regulator and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.Immunological reviews · 2019Review
- Microbiome and Autoimmune Uveitis.Frontiers in immunology · 2019Review
- Insights into immune tolerance from AIRE deficiency.Current opinion in immunology · 2017Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Studies of the genetic factors associated with human autoimmune disease suggest a multigenic origin of susceptibility; however, how these factors interact and through which tolerance pathways they operate generally remain to be defined. One key checkpoint occurs through the activity of the autoimmune regulator AIRE, which promotes central T cell tolerance. Recent reports have described a variety of dominant-negative AIRE mutations that likely contribute to human autoimmunity to a greater extent than previously thought. In families with these mutations, the penetrance of autoimmunity is incomplete, suggesting that other checkpoints play a role in preventing autoimmunity. Here, we tested whether a defect in LYN, an inhibitory protein tyrosine kinase that is implicated in systemic autoimmunity, could combine with an Aire mutation to provoke organ-specific autoimmunity. Indeed, mice with a dominant-negative allele of Aire and deficiency in LYN spontaneously developed organ-specific autoimmunity in the eye. We further determined that a small pool of retinal protein-specific T cells escaped thymic deletion as a result of the hypomorphic Aire function and that these cells also escaped peripheral tolerance in the presence of LYN-deficient dendritic cells, leading to highly destructive autoimmune attack. These findings demonstrate how 2 distinct tolerance pathways can synergize to unleash autoimmunity and have implications for the genetic susceptibility of autoimmune 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.