ArticleArthritis & rheumatology (Hoboken, N.J.)2016
Epigenetic Reprogramming in Naive CD4+ T Cells Favoring T Cell Activation and Non-Th1 Effector T Cell Immune Response as an Early Event in Lupus Flares.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis 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
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- The role of microRNAs and long non-coding RNAs in epigenetic regulation of T cells: implications for autoimmunity.Frontiers in immunology · 2025Pooled it
- Differential transcriptional and epigenetic signatures in CD4Journal of translational autoimmunity · 2026Article
- A novel epigenetic regulation of JAM-A by EZH2-DNMT3A cascade contributes to T cell adhesion via the activation of Rap1a in lupus patients.Journal of translational autoimmunity · 2026Article
- DNA Methylation Profiling in Childhood-Onset Lupus Reveals Distinct Epigenetic Clusters and Suggests Epigenetic Drivers of Disease Activity.medRxiv : the preprint server for health sciences · 2025Article
- Immunometabolism in systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Associations between Blood DNA Methylation and Histopathologic Features in Lupus Nephritis.Kidney360 · 2025Article
- Identification of Potential Drug Targets for Immunoglobulin A Nephropathy: A Mendelian Randomization Study.Biomedicines · 2025Article
- Angiotensin receptor blockers modulate the lupus CD4+ T cell epigenome characterized by TNF family-linked signaling.JCI insight · 2024Article
- Inducible deletion ofiScience · 2024Article
- Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders.Signal transduction and targeted therapy · 2024Review
- DNA methylation and whole-genome transcription analysis in CD4Clinical epigenetics · 2024Article
- Article
- DNA methylation in human diseases.Heliyon · 2024Review
- Methylation of T and B Lymphocytes in Autoimmune Rheumatic Diseases.Clinical reviews in allergy & immunology · 2024Review
- Ezh2 Knockout in B Cells Impairs Plasmablast Differentiation and Ameliorates Lupus-like Disease in MRL/lpr Mice.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Decipher the Immunopathological Mechanisms and Set Up Potential Therapeutic Strategies for Patients with Lupus Nephritis.International journal of molecular sciences · 2023Review
- Quantifying the impact of gut microbiota on inflammation and hypertensive organ damage.Cardiovascular research · 2023Article
- Shaping Heterogeneity of Naive CD8Immune network · 2023Review
- T-helper cells flexibility: the possibility of reprogramming T cells fate.Frontiers in immunology · 2023Review
- Methylation ofDiagnostics (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveSystemic lupus erythematosus (SLE) is a relapsing autoimmune disease that affects multiple organ systems. T cells play an important role in the pathogenesis of lupus; however, early T cell events triggering disease flares are incompletely understood. This study was undertaken to examine DNA methylation in naive CD4+ T cells from lupus patients to determine if epigenetic remodeling in CD4+ T cells is an early event in lupus flares.
methodsA total of 74 lupus patients with an SLE Disease Activity Index score of 0-18 were included. Naive CD4+ T cells were isolated from peripheral blood samples, and DNA was extracted for genome-wide methylation assessment. RNA was also extracted from a subset of patients to determine the relationship between epigenetic changes and transcription activity using RNA sequencing and microRNA arrays.
resultsWe demonstrated that naive CD4+ T cells in lupus undergo an epigenetic proinflammatory shift, implicating effector T cell responses in lupus flare. This epigenetic landscape change occurs without changes in expression of the corresponding genes, poises naive CD4+ T cells for Th2, Th17, and follicular helper T cell immune responses, and opposes inhibitory transforming growth factor β signaling. Bioinformatics analyses indicate that the epigenetic modulator EZH2 might play an important role in shifting the epigenetic landscape, with increased disease activity in lupus naive CD4+ T cells. Further, the expression of microRNA-26a, which is sensitive to glucose availability and targets EZH2, was negatively correlated with disease activity in lupus patients.
conclusionAn epigenetic landscape shift in naive CD4+ T cells that favors T cell activation and non-Th1 immune responses predates transcription activity and correlates with lupus activity. A role for EZH2 dysregulation in triggering lupus flares warrants further investigation.
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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.