ArticleArthritis & rheumatology (Hoboken, N.J.)2014
Oxidative stress, T cell DNA methylation, and lupus.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Emerging Epigenetic Role of CD8+T Cells in Autoimmune Diseases: A Systematic Review.Frontiers in immunology · 2019Pooled it
- Oxidative Stress, Environmental Pollutants, Aging, and Epigenetic Regulation: Mechanistic Insights and Biomarker Advances.Antioxidants (Basel, Switzerland) · 2026Review
- Review
- Immunopathogenesis and Therapeutics of Systemic Lupus Erythematosus: an Integrative Review.Clinical reviews in allergy & immunology · 2025Review
- Autoimmune Gastritis andInternational journal of molecular sciences · 2025Review
- Plasma cell-free DNA genome-wide methylation profiling enables detection and activity assessment in systemic lupus erythematosus.Frontiers in immunology · 2025Article
- American College of Rheumatology White Paper: The Effects of Climate Change on Rheumatic Conditions-An Evolving Landscape and a Path Forward.Arthritis & rheumatology (Hoboken, N.J.) · 2024Review
- Methylation of T and B Lymphocytes in Autoimmune Rheumatic Diseases.Clinical reviews in allergy & immunology · 2024Review
- Effect of DNA methylation on the osteogenic differentiation of mesenchymal stem cells: concise review.Frontiers in genetics · 2024Review
- Article
- Age-related mechanisms in the context of rheumatic disease.Nature reviews. Rheumatology · 2022Review
- Dynamics of Methylation of CpG Sites Associated With Systemic Lupus Erythematosus Subtypes in a Longitudinal Cohort.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling.Research square · 2022Article
- SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling.bioRxiv : the preprint server for biology · 2022Article
- Lupus Susceptibility Loci Predispose Mice to Clonal Lymphocytic Responses and Myeloid Expansion.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- The Role of Oxidative Stress in Epigenetic Changes Underlying Autoimmunity.Antioxidants & redox signaling · 2022Review
- T Cell Homeostatic Proliferation Promotes a Redox State That Drives Metabolic and Epigenetic Upregulation of Inflammatory Pathways in Lupus.Antioxidants & redox signaling · 2022Review
- Epigenetic Alterations in Immune Cells of Systemic Lupus Erythematosus and Therapeutic Implications.Cells · 2022Review
- Lupus nephritis: The regulatory interplay between epigenetic and MicroRNAs.Frontiers in physiology · 2022Review
- The relationship of polluted air and drinking water sources with the prevalence of systemic lupus erythematosus: a provincial population-based study.Scientific reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
objectiveLupus develops when genetically predisposed people encounter environmental agents, such as ultraviolet 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 inhibiting DNA methylation in CD4+ T cells by blocking ERK pathway signaling is sufficient to alter gene expression, and that the modified cells cause lupus-like autoimmunity in mice. We also reported that T cells from patients with active lupus have decreased ERK pathway signaling, have decreased DNA methylation, and overexpress genes normally suppressed by DNA methylation. This study was undertaken to test whether oxidizing agents decrease ERK pathway signaling in T cells, decrease DNA methyltransferase levels, and cause demethylation and overexpression of T cell genes similar to that found in T cells from patients with active lupus.
methodsCD4+ T cells were treated with the oxidizers H2 O2 or ONOO(-) . Effects on ERK pathway signaling were measured by immunoblotting, DNA methyltransferase 1 (DNMT-1) levels were measured by reverse transcriptase-polymerase chain reaction (RT-PCR), and the methylation and expression of T cell genes were measured using flow cytometry, RT-PCR, and bisulfite sequencing.
resultsH2 O2 and ONOO(-) inhibited ERK pathway signaling in T cells by inhibiting the upstream regulator protein kinase Cδ, decreased DNMT-1 levels, and caused demethylation and overexpression of genes previously shown to be suppressed by DNA methylation in T cells from patients with active lupus.
conclusionOur findings indicate that oxidative stress may contribute to human lupus flares by inhibiting ERK pathway signaling in T cells to decrease DNMT-1 and cause DNA demethylation.
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Registered trials
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