ArticlePloS one2014
Lymphocyte Activation Gene-3 (LAG-3) negatively regulates environmentally-induced autoimmunity.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 3 of them syntheses that pooled it.
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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
33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Prognostic Value of Lymphocyte-Activation Gene 3 (LAG3) in Cancer: A Meta-Analysis.Frontiers in oncology · 2019Pooled it
- Pooled it
- LAG3 Gene Therapy Attenuates Autoimmune Uveitis by Regulating the PI3K/Akt Signaling Pathway.Investigative ophthalmology & visual science · 2026Article
- Regulatory T Cells and IFNγ in Mercury-Induced Autoimmunity: Insights from Adoptive Transfer in B10.S Mice.Biology · 2026Article
- PD-1, BTLA and TIGIT as therapeutic targets for rheumatic disease.Nature reviews. Rheumatology · 2026Review
- LAG3 regulates antibody responses in a murine model of kidney transplantation.The Journal of clinical investigation · 2025Article
- Unlocking therapeutic potential: Targeting lymphocyte activation Gene-3 (LAG-3) with fibrinogen-like protein 1 (FGL1) in systemic lupus erythematosus.Journal of translational autoimmunity · 2024Review
- LAG-3-An incompletely understood target in cancer therapy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Surface Immune Checkpoints as Potential Biomarkers in Physiological Pregnancy and Recurrent Pregnancy Loss.International journal of molecular sciences · 2024Article
- Soluble immune checkpoints are elevated in patients with primary biliary cholangitis.European journal of medical research · 2023Article
- Immune checkpoint inhibitor-associated toxicity in advanced non-small cell lung cancer: An updated understanding of risk factors.Frontiers in immunology · 2023Review
- Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future.Frontiers in immunology · 2023Review
- Lymphocyte Activation Gene 3 Single-Nucleotide Polymorphisms in Bone Marrow Failure Diseases.Analytical cellular pathology (Amsterdam) · 2022Article
- Seven mysteries of LAG-3: a multi-faceted immune receptor of increasing complexity.Immunotherapy advances · 2022Review
- Immune Checkpoints, a Novel Class of Therapeutic Targets for Autoimmune Diseases.Frontiers in immunology · 2021Review
- Decreased LAG3 expression on T effector cells and regulatory T cells in SAA.International journal of hematology · 2020Article
- Inhibitory receptor agonists: the future of autoimmune disease therapeutics?Current opinion in immunology · 2020Review
- Molecular, clinicopathological, and immune correlates of LAG3 promoter DNA methylation in melanoma.EBioMedicine · 2020Article
- LAG-3: from molecular functions to clinical applications.Journal for immunotherapy of cancer · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Environmental factors including drugs, mineral oils and heavy metals such as lead, gold and mercury are triggers of autoimmune diseases in animal models or even in occupationally exposed humans. After exposure to subtoxic levels of mercury (Hg), genetically susceptible strains of mice develop an autoimmune disease characterized by the production of highly specific anti-nucleolar autoantibodies, hyperglobulinemia and nephritis. However, mice can be tolerized to the disease by a single low dose administration of Hg. Lymphocyte Activation Gene-3 (LAG-3) is a CD4-related, MHC-class II binding molecule expressed on activated T cells and NK cells which maintains lymphocyte homeostatic balance via various inhibitory mechanisms. In our model, administration of anti-LAG-3 monoclonal antibody broke tolerance to Hg resulting in autoantibody production and an increase in serum IgE level. In addition, LAG-3-deficient B6.SJL mice not only had increased susceptibility to Hg-induced autoimmunity but were also unresponsive to tolerance induction. Conversely, adoptive transfer of wild-type CD4(+) T cells was able to partially rescue LAG-3-deficient mice from the autoimmune disease. Further, in LAG-3-deficient mice, mercury elicited higher amounts of IL-6, IL-4 and IFN-γ, cytokines known to play a critical role in mercury-induced autoimmunity. Therefore, we conclude that LAG-3 exerts an important regulatory effect on autoimmunity elicited by a common environmental pollutant.
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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.