ArticleThe Journal of clinical investigation2013
Medullary thymic epithelial cell depletion leads to autoimmune hepatitis.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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.
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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
43 citing papers in PubMed, 67 citations in OpenAlex.
- Aire and Fezf2 Shape the Medullary Thymic Epithelial Cell Immunopeptidome for Central Tolerance.Immunology · 2026Review
- Experimental Models of Autoimmune Hepatitis: Disease Fidelity and Translational Relevance.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- TRAF6, a gga-miR-7b Target, PromotesBiomolecules · 2026Article
- Lyn restrains lupus via kinase-independent mechanisms that limit Toll-like receptor activation and type I interferon responsiveness.Science advances · 2025Article
- Endogenous thymic regeneration: restoring T cell production following injury.Nature reviews. Immunology · 2025Review
- The Proteostasis of Thymic Stromal Cells in Health and Diseases.The protein journal · 2024Review
- Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both?Molecular and cellular pediatrics · 2024Review
- Mechanism study of ubiquitination in T cell development and autoimmune disease.Frontiers in immunology · 2024Review
- The Function of Ubiquitination in T-Cell Development.Advances in experimental medicine and biology · 2024Review
- Impaired central tolerance induces changes in the gut microbiota that exacerbate autoimmune hepatitis.Journal of autoimmunity · 2022Article
- Chinese medicine in the treatment of autoimmune hepatitis: Progress and future opportunities.Animal models and experimental medicine · 2022Review
- Autoimmmune hepatitis.Cellular & molecular immunology · 2022Review
- Type 2 autoimmune hepatitis: Genetic susceptibility.Frontiers in immunology · 2022Review
- Protein ubiquitination in T cell development.Frontiers in immunology · 2022Review
- Article
- Pathogenesis of Autoimmune Hepatitis-Cellular and Molecular Mechanisms.International journal of molecular sciences · 2021Review
- Failure of thymic deletion and instability of autoreactive Tregs drive autoimmunity in immune-privileged liver.JCI insight · 2021Article
- Dysfunctional Immune Regulation in Autoimmune Hepatitis: From Pathogenesis to Novel Therapies.Frontiers in immunology · 2021Review
- Acute severe autoimmune hepatitis with anti-rods and rings autoantibodies; literature first evidence.Gastroenterology and hepatology from bed to bench · 2021Article
- Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
TRAF6, an E3 ubiquitin protein ligase, plays a critical role in T cell tolerance by regulating medullary thymic epithelial cell (mTEC) development. mTECs regulate T cell tolerance by ectopically expressing self-antigens and eliminating autoreactive T cells in the thymus. Here we show that mice with mTEC depletion due to conditional deletion of Traf6 expression in murine thymic epithelial cells (Traf6ΔTEC mice) showed a surprisingly narrow spectrum of autoimmunity affecting the liver. The liver inflammation in Traf6ΔTEC mice exhibited all the histological and immunological characteristics of human autoimmune hepatitis (AIH). The role of T cells in AIH establishment was supported by intrahepatic T cell population changes and AIH development after transfer of liver T cells into immunodeficient mice. Despite a 50% reduction in natural Treg thymic output, peripheral tolerance in Traf6ΔTEC mice was normal, whereas compensatory T regulatory mechanisms were evident in the liver of these animals. These data indicate that mTECs exert a cell-autonomous role in central T cell tolerance and organ-specific autoimmunity, but play a redundant role in peripheral tolerance. These findings also demonstrate that Traf6ΔTEC mice are a relevant model with which to study the pathophysiology of AIH, as well as autoantigen-specific T cell responses and regulatory mechanisms underlying this 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.