ArticleThe Journal of experimental medicine2008
Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance.
Article in The Journal of experimental medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed, 226 citations in OpenAlex.
- Altered expression of autoimmune regulator in infant down syndrome thymus, a possible contributor to an autoimmune phenotype.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Article
- Integrative Multiomic Classification Reveals Distinct Origins and Evolutionary Trajectories of Thymic Epithelial Tumors.Cancer research · 2026Article
- Beyond cysts - organization of epithelial networks in the murine thymus.Journal of cell science · 2025Article
- 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
- It's Time to Unite: Diversity and Coordination of Thymic Stromal Cells for T Cell Selection and Organ Integrity.Immunological reviews · 2025Review
- Thymic Interferons: A Little Goes a Long Way.Immunological reviews · 2025Review
- Antigen presentation for central tolerance induction.Nature reviews. Immunology · 2025Review
- Thymic Crosstalk: An Overview of the Complex Cellular Interactions that Control the Establishment of T-Cell Tolerance.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
- The Ins and Outs of Thymic Epithelial Cell Differentiation and Function.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
- Transcript splicing optimizes the thymic self-antigen repertoire to suppress autoimmunity.The Journal of clinical investigation · 2024Article
- Primary and secondary defects of the thymus.Immunological reviews · 2024Review
- Assembling the thymus medulla: Development and function of epithelial cell heterogeneity.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Article
- Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis.Frontiers in immunology · 2024Review
- Autoimmunity in thymic epithelial tumors: a not yet clarified pathologic paradigm associated with several unmet clinical needs.Frontiers in immunology · 2024Review
- Learning the Autoimmune Pathogenesis Through the Study of Aire.Advances in experimental medicine and biology · 2024Article
- Novel Insights into the Autoimmunity from the Genetic Approach of the Human Disease.Advances in experimental medicine and biology · 2024Article
- Preclinical Study in Mouse Thymus and Thymocytes: Effects of Treatment with a Combination of Sodium Dichloroacetate and Sodium Valproate on Infectious Inflammation Pathways.Pharmaceutics · 2023Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The roles of autoimmune regulator (Aire) in the expression of the diverse arrays of tissue-restricted antigen (TRA) genes from thymic epithelial cells in the medulla (medullary thymic epithelial cells [mTECs]) and in organization of the thymic microenvironment are enigmatic. We approached this issue by creating a mouse strain in which the coding sequence of green fluorescent protein (GFP) was inserted into the Aire locus in a manner allowing concomitant disruption of functional Aire protein expression. We found that Aire(+) (i.e., GFP(+)) mTECs were the major cell types responsible for the expression of Aire-dependent TRA genes such as insulin 2 and salivary protein 1, whereas Aire-independent TRA genes such as C-reactive protein and glutamate decarboxylase 67 were expressed from both Aire(+) and Aire(-) mTECs. Remarkably, absence of Aire from mTECs caused morphological changes together with altered distribution of mTECs committed to Aire expression. Furthermore, we found that the numbers of mTECs that express involucrin, a marker for terminal epidermal differentiation, were reduced in Aire-deficient mouse thymus, which was associated with nearly an absence of Hassall's corpuscle-like structures in the medulla. Our results suggest that Aire controls the differentiation program of mTECs, thereby organizing the global mTEC integrity that enables TRA expression from terminally differentiated mTECs in the thymic microenvironment.
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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.