ArticleThe Journal of experimental medicine2009
Neonatal tolerance revisited: a perinatal window for Aire control of autoimmunity.
Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 172 citations in OpenAlex.
- KLF2 controls thymic epithelial cell homeostasis, impacting regulatory T cell development and immune tolerance.iScience · 2026Article
- Dual T cell receptor expression provides intrinsic advantage for agonist selection of thymic FoxP3+ regulatory T cells (Tregs) in the neonatal thymus.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Flt3L-Derived Antigen-Presenting Cell Transfer in Neonatal NOD Mice Reduces the Incidence of Type 1 Diabetes.Diabetes · 2026Article
- Low ZAP70 expression drives neonatal TNature immunology · 2025Article
- Intrathymic Regulation of Dendritic Cell Subsets and Their Contributions to Central Tolerance.Immunological reviews · 2025Review
- T cell exhaustion in pediatric B-ALL: current knowledge and future perspectives.Frontiers in 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 Ins and Outs of Thymic Epithelial Cell Differentiation and Function.Advances in experimental medicine and biology · 2025Review
- Aire in Autoimmunity.Annual review of immunology · 2024Review
- Foxo3 regulates cortical and medullary thymic epithelial cell homeostasis with implications in T cell development.Cell death & disease · 2024Article
- Encapsulation and immune protection for type 1 diabetes cell therapy.Advanced drug delivery reviews · 2024Review
- Extraislet expression of islet antigen boosts T cell exhaustion to partially prevent autoimmune diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Lymph node stromal cell responses to perinatal T cell waves, a temporal atlas.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
- Revisiting Aire and tissue-restricted antigens at single-cell resolution.Frontiers in immunology · 2023Review
- Thymic mimetic cells: tolerogenic masqueraders.Trends in immunology · 2022Review
- Article
- Fetal-placental antigens and the maternal immune system: Reproductive immunology comes of age.Immunological reviews · 2022Review
- PD-1 cooperates with AIRE-mediated tolerance to prevent lethal autoimmune disease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mechanisms of Direct and Indirect Presentation of Self-Antigens in the Thymus.Frontiers in immunology · 2022Review
39 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
There has long been conceptual and experimental support for, but also challenges to, the notion that the initial period of the immune system's development is particularly important for the establishment of tolerance to self. The display of self-antigens by thymic epithelial cells is key to inducing tolerance in the T lymphocyte compartment, a process enhanced by the Aire transcription factor. Using a doxycycline-regulated transgene to target Aire expression to the thymic epithelium, complementing the Aire knockout in a temporally controlled manner, we find that Aire is essential in the perinatal period to prevent the multiorgan autoimmunity that is typical of Aire deficiency. Surprisingly, Aire could be shut down soon thereafter and remain off for long periods, with few deleterious consequences. The lymphopenic state present in neonates was a factor in this dichotomy because inducing lymphopenia during Aire turnoff in adults recreated the disease, which, conversely, could be ameliorated by supplementing neonates with adult lymphocytes. In short, Aire expression during the perinatal period is both necessary and sufficient to induce long-lasting tolerance and avoid autoimmunity. Aire-controlled mechanisms of central tolerance are largely dispensable in the adult, as a previously tolerized T cell pool can buffer newly generated autoreactive T cells that might emerge.
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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.