ArticleProceedings of the National Academy of Sciences of the United States of America2008
Ectopic expression of peripheral-tissue antigens in the thymic epithelium: probabilistic, monoallelic, misinitiated.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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
73 citing papers in PubMed, 125 citations in OpenAlex.
- Role of PRC2 in the stochastic expression of Aire target genes and development of mimetic cells in the thymus.The Journal of experimental medicine · 2025Article
- Thymic Interferons: A Little Goes a Long Way.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
- The Thymus as a Mirror of the Body's Gene Expression.Advances in experimental medicine and biology · 2025Review
- Thymic Mimetic Cells: Ontogeny as Immunology.Annual review of cell and developmental biology · 2024Review
- Aire in Autoimmunity.Annual review of immunology · 2024Review
- Learning the Autoimmune Pathogenesis Through the Study of Aire.Advances in experimental medicine and biology · 2024Article
- Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis.Frontiers in immunology · 2024Review
- Hnf4 activates mimetic-cell enhancers to recapitulate gut and liver development within the thymus.The Journal of experimental medicine · 2023Article
- Investigating Thymic Epithelial Cell Diversity Using Systems Biology.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Revisiting Aire and tissue-restricted antigens at single-cell resolution.Frontiers in immunology · 2023Review
- Ehf and Fezf2 regulate late medullary thymic epithelial cell and thymic tuft cell development.Frontiers in immunology · 2023Article
- Thymic mimetic cells: tolerogenic masqueraders.Trends in immunology · 2022Review
- Transcriptomic diversity in human medullary thymic epithelial cells.Nature communications · 2022Article
- Article
- AIRE in context: Leveraging chromatin plasticity to trigger ectopic gene expression.Immunological reviews · 2022Review
- Mechanisms of Direct and Indirect Presentation of Self-Antigens in the Thymus.Frontiers in immunology · 2022Review
- Aire regulates chromatin looping by evicting CTCF from domain boundaries and favoring accumulation of cohesin on superenhancers.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Indispensable epigenetic control of thymic epithelial cell development and function by polycomb repressive complex 2.Nature communications · 2021Article
- Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence.Frontiers in immunology · 2021Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Thymic medullary epithelial cells (MECs) express a broad repertoire of peripheral-tissue antigens (PTAs), many of which depend on the transcriptional regulatory factor Aire. Although Aire is known to be critically important for shaping a self-tolerant T cell repertoire, its role in MEC maturation and function remains poorly understood. Using a highly sensitive and reproducible single-cell PCR assay, we demonstrate that individual Aire-expressing MECs transcribe a subset of PTA genes in a probabilistic fashion, with no signs of preferential coexpression of genes characteristic of particular extrathymic epithelial cell lineages. In addition, Aire-dependent PTA genes in MECs are transcribed monoallelically or biallelically in a stochastic pattern, in contrast to the usually biallelic transcription of these same genes in the relevant peripheral cells or of Aire-independent genes in MECs. Expression of PTA genes in MECs depends on transcriptional regulators and uses transcriptional start sites different from those used in peripheral cells. These findings support the "terminal differentiation" model of Aire function: as MECs mature, they transcribe more and more PTA genes, culminating in a cell population that is both capable of presenting antigens (MHCII(hi), CD80(hi)) and can draw on a large repertoire of antigens to present.
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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.