ArticleThe Journal of clinical investigation2008
Ectopic expression of neural autoantigen in mouse liver suppresses experimental autoimmune neuroinflammation by inducing antigen-specific Tregs.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 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
92 citing papers in PubMed, 161 citations in OpenAlex.
- Selective decrease of donor-reactive TScience translational medicine · 2022Trial
- Emerging Immune-Based Therapeutic Strategies in Hepatocellular Carcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- The bacteroidal metabolite O-LysoPE facilitates hepatocyte-mediated immunosuppression in autoimmune hepatitis.Nature communications · 2026Article
- Review
- Liver-Targeting Nanoplatforms for the Induction of Immune Tolerance.Nanomaterials (Basel, Switzerland) · 2023Review
- Mucins Shed from the Laminated Layer in Cystic Echinococcosis Are Captured by Kupffer Cells via the Lectin Receptor Clec4F.Infection and immunity · 2023Article
- Immunology of a unique biological structure: the Echinococcus laminated layer.Protein & cell · 2023Article
- Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers.Translational gastroenterology and hepatology · 2023Review
- Harnessing the liver to induce antigen-specific immune tolerance.Seminars in immunopathology · 2022Review
- Regulatory T Cell Therapeutics for Neuroinflammatory Disorders.Critical reviews in immunology · 2022Review
- Animal Models for Autoimmune Hepatitis: Are Current Models Good Enough?Frontiers in immunology · 2022Review
- Review
- Cas9-directed immune tolerance in humans-a model to evaluate regulatory T cells in gene therapy?Gene therapy · 2021Review
- The Liver and the Hepatic Immune Response inPathogens (Basel, Switzerland) · 2021Review
- Functional heterogeneity of CD4Seminars in immunopathology · 2021Review
- Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy.Cellular & molecular immunology · 2021Review
- Failure of thymic deletion and instability of autoreactive Tregs drive autoimmunity in immune-privileged liver.JCI insight · 2021Article
- Antigen-Specific Treatment Modalities in MS: The Past, the Present, and the Future.Frontiers in immunology · 2021Review
- Understanding, predicting and achieving liver transplant tolerance: from bench to bedside.Nature reviews. Gastroenterology & hepatology · 2020Review
- Treg Enhancing Therapies to Treat Autoimmune Diseases.International journal of molecular sciences · 2020Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
Tregs are important mediators of immune tolerance to self antigens, and it has been suggested that Treg inactivation may cause autoimmune disease. Therefore, immunotherapy approaches that aim to restore or expand autoantigen-specific Treg activity might be beneficial for the treatment of autoimmune disease. Here we report that Treg-mediated suppression of autoimmune disease can be achieved in vivo by taking advantage of the ability of the liver to promote immune tolerance. Expression of the neural autoantigen myelin basic protein (MBP) in the liver was accomplished stably in liver-specific MBP transgenic mice and transiently using gene transfer to liver cells in vivo. Such ectopic MBP expression induced protection from autoimmune neuroinflammation in a mouse model of multiple sclerosis. Protection from autoimmunity was mediated by MBP-specific CD4+CD25+Foxp3+ Tregs, as demonstrated by the ability of these cells to prevent disease when adoptively transferred into nontransgenic mice and to suppress conventional CD4+CD25- T cell proliferation after antigen-specific stimulation with MBP in vitro. The generation of MBP-specific CD4+CD25+Foxp3+ Tregs in vivo depended on expression of MBP in the liver, but not in skin, and occurred by TGF-beta-dependent peripheral conversion from conventional non-Tregs. Our findings indicate that autoantigen expression in the liver may generate autoantigen-specific Tregs. Thus, targeting of autoantigens to hepatocytes may be a novel approach to prevention or treatment of autoimmune diseases.
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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.