ArticleThe Journal of experimental medicine2015
Identification of a novel cis-regulatory element essential for immune tolerance.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 56 citations in OpenAlex.
- RORγtScience immunology · 2026Article
- Aire Mutations and Autoimmune Diseases.Advances in experimental medicine and biology · 2025Review
- The Autoimmune Regulator (AIRE) Gene, The Master Activator of Self-Antigen Expression in the Thymus.Advances in experimental medicine and biology · 2025Review
- A deep intronic splice-alteringScience translational medicine · 2024Article
- Aire in Autoimmunity.Annual review of immunology · 2024Review
- Mitochondrial extracellular vesicles, autoimmunity and myocarditis.Frontiers in immunology · 2024Review
- Direct and indirect RANK and CD40 signaling regulate the maintenance of thymic epithelial cell frequency and properties in the adult thymus.Frontiers in immunology · 2024Article
- Novel Insights into the Autoimmunity from the Genetic Approach of the Human Disease.Advances in experimental medicine and biology · 2024Article
- A distinct human cell type expressing MHCII and RORγt with dual characteristics of dendritic cells and type 3 innate lymphoid cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Insm1 regulates mTEC development and immune tolerance.Cellular & molecular immunology · 2023Article
- Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency.Nature · 2023Article
- Article
- Transcriptional and epigenetic regulation in thymic epithelial cells.Immunological reviews · 2022Review
- AIRE in context: Leveraging chromatin plasticity to trigger ectopic gene expression.Immunological reviews · 2022Review
- Single-cell multiomics defines tolerogenic extrathymic Aire-expressing populations with unique homology to thymic epithelium.Science immunology · 2021Article
- Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE autoregulation.The Journal of experimental medicine · 2021Article
- Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy.Frontiers in pediatrics · 2021Review
- TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2021Review
- Type II Cytokines Fine-Tune Thymic T Cell Selection to Offset Murine Central Nervous System Autoimmunity.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Toll-like receptor signaling in thymic epithelium controls monocyte-derived dendritic cell recruitment and Treg generation.Nature communications · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Thymic central tolerance is essential to preventing autoimmunity. In medullary thymic epithelial cells (mTECs), the Autoimmune regulator (Aire) gene plays an essential role in this process by driving the expression of a diverse set of tissue-specific antigens (TSAs), which are presented and help tolerize self-reactive thymocytes. Interestingly, Aire has a highly tissue-restricted pattern of expression, with only mTECs and peripheral extrathymic Aire-expressing cells (eTACs) known to express detectable levels in adults. Despite this high level of tissue specificity, the cis-regulatory elements that control Aire expression have remained obscure. Here, we identify a highly conserved noncoding DNA element that is essential for Aire expression. This element shows enrichment of enhancer-associated histone marks in mTECs and also has characteristics of being an NF-κB-responsive element. Finally, we find that this element is essential for Aire expression in vivo and necessary to prevent spontaneous autoimmunity, reflecting the importance of this regulatory DNA element in promoting immune tolerance.
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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.