ArticleJournal of autoimmunity2015
CD4(+) T cells epigenetically modified by oxidative stress cause lupus-like autoimmunity in mice.
Article in Journal of autoimmunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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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Who cites it
38 citing papers in PubMed, 77 citations in OpenAlex.
- Review
- Immunopathogenesis and Therapeutics of Systemic Lupus Erythematosus: an Integrative Review.Clinical reviews in allergy & immunology · 2025Review
- Association between phthalate exposure and rash eczema disease: based on NHANES 2005-2006.Archives of dermatological research · 2025Article
- The climate emergency for rheumatologists: where do we stand?Clinical rheumatology · 2025Review
- Immune pathogenesis of idiopathic granulomatous mastitis: from etiology toward therapeutic approaches.Frontiers in immunology · 2024Review
- Ozone Pollution, Oxidative Stress, Regulatory T Cells and Antioxidants.Antioxidants (Basel, Switzerland) · 2022Review
- The Role of Oxidative Stress in Epigenetic Changes Underlying Autoimmunity.Antioxidants & redox signaling · 2022Review
- Epigenetic Alterations in Immune Cells of Systemic Lupus Erythematosus and Therapeutic Implications.Cells · 2022Review
- 3-hydroxy butyrate dehydrogenase 2 deficiency aggravates systemic lupus erythematosus progression in a mouse model by promoting CD40 ligand demethylation.Bioengineered · 2022Article
- Cancer and Autoimmune Diseases: A Tale of Two Immunological Opposites?Frontiers in immunology · 2022Article
- The relationship of polluted air and drinking water sources with the prevalence of systemic lupus erythematosus: a provincial population-based study.Scientific reports · 2021Article
- DNA Methylation Sustains "Inflamed" Memory of Peripheral Immune Cells Aggravating Kidney Inflammatory Response in Chronic Kidney Disease.Frontiers in physiology · 2021Review
- TGF-β1 Signaling: Immune Dynamics of Chronic Kidney Diseases.Frontiers in medicine · 2021Review
- Selective DNA Demethylation Accompanies T Cell Homeostatic Proliferation and Gene Regulation in Lupus-ProneImmunoHorizons · 2020Article
- DNA methylation changes on immune cells in Systemic Lupus Erythematosus.Autoimmunity · 2020Review
- T cell Metabolism in Lupus.Immunometabolism · 2020Article
- Review
- Association between activity and genotypes of paraoxonase1 LMolecular biology reports · 2019Article
- Continuous Developmental and Early Life Trichloroethylene Exposure Promoted DNA Methylation Alterations in Polycomb Protein Binding Sites in Effector/Memory CD4Frontiers in immunology · 2019Article
- Oxidative stress and dietary micronutrient deficiencies contribute to overexpression of epigenetically regulated genes by lupus T cells.Clinical immunology (Orlando, Fla.) · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Lupus develops when genetically predisposed people encounter environmental agents such as UV light, silica, infections and cigarette smoke that cause oxidative stress, but how oxidative damage modifies the immune system to cause lupus flares is unknown. We previously showed that oxidizing agents decreased ERK pathway signaling in human T cells, decreased DNA methyltransferase 1 and caused demethylation and overexpression of genes similar to those from patients with active lupus. The current study tested whether oxidant-treated T cells can induce lupus in mice. We adoptively transferred CD4(+) T cells treated in vitro with oxidants hydrogen peroxide or nitric oxide or the demethylating agent 5-azacytidine into syngeneic mice and studied the development and severity of lupus in the recipients. Disease severity was assessed by measuring anti-dsDNA antibodies, proteinuria, hematuria and by histopathology of kidney tissues. The effect of the oxidants on expression of CD40L, CD70, KirL1 and DNMT1 genes and CD40L protein in the treated CD4(+) T cells was assessed by Q-RT-PCR and flow cytometry. H2O2 and ONOO(-) decreased Dnmt1 expression in CD4(+) T cells and caused the upregulation of genes known to be suppressed by DNA methylation in patients with lupus and animal models of SLE. Adoptive transfer of oxidant-treated CD4(+) T cells into syngeneic recipients resulted in the induction of anti-dsDNA antibody and glomerulonephritis. The results show that oxidative stress may contribute to lupus disease by inhibiting ERK pathway signaling in T cells leading to DNA demethylation, upregulation of immune genes and autoreactivity.
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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.