ArticleThe Journal of biological chemistry2012
cAMP-responsive element modulator α (CREMα) contributes to decreased Notch-1 expression in T cells from patients with active systemic lupus erythematosus (SLE).
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- PPAR-α Agonist Suppresses Expression of Immune Mediators in B Cells in a Murine Model of Systemic Lupus Erythematosus.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Increased Expression of NOTCH-1 and T Helper Cell Transcription Factors in Patients with Acquired Aplastic Anemia.Iranian biomedical journal · 2023Article
- Innate and adaptive immune abnormalities underlying autoimmune diseases: the genetic connections.Science China. Life sciences · 2023Review
- Article
- Decreased SUV39H1 at the promoter region leads to increased CREMα and accelerates autoimmune response in CD4Clinical epigenetics · 2022Article
- Macrophage Polarization and Plasticity in Systemic Lupus Erythematosus.Frontiers in immunology · 2021Review
- Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases.Frontiers in immunology · 2021Review
- Hypomethylation of Notch1 DNA is associated with the occurrence of uveitis.Clinical and experimental immunology · 2020Article
- Article
- Bone marrow transplant-induced alterations in Notch signaling promote pathologic Th17 responses to γ-herpesvirus infection.Mucosal immunology · 2018Article
- Asiatic acid attenuates lipopolysaccharide-induced injury by suppressing activation of the Notch signaling pathway.Oncotarget · 2018Article
- The Potential Role of Trained Immunity in Autoimmune and Autoinflammatory Disorders.Frontiers in immunology · 2018Review
- [Effect of aberrant H3K27me3 modification in promoter regions on cAMP response element modulator α expression in CD4Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2017Article
- Article
- Epigenetics in SLE.Current rheumatology reports · 2017Review
- DNA methylation in systemic lupus erythematosus.Epigenomics · 2017Review
- SLE-Associated Defects Promote Altered T Cell Function.Critical reviews in immunology · 2017Review
- Correlation of Notch1/Hes1 Genes Expression Levels in Egyptian Paediatric Patients with Newly Diagnosed and Persistent Primary Immune(Idiopathic) Thrombocytopenic Purpura.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2016Article
- Notch-Hes-1 axis controls TLR7-mediated autophagic death of macrophage via induction of P62 in mice with lupus.Cell death & disease · 2016Article
- Whole-genome transcription and DNA methylation analysis of peripheral blood mononuclear cells identified aberrant gene regulation pathways in systemic lupus erythematosus.Arthritis research & therapy · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Notch signaling constitutes an evolutionarily conserved pathway that transduces signals between neighboring cells and determines major decisions in cell proliferation, survival, and differentiation. Notch signaling has been shown to play a pivotal role during T cell lineage determination. T lymphocytes from patients with systemic lupus erythematosus (SLE) display a severely altered phenotype with several molecular and functional aberrations, including defective capacities to up-regulate Notch-1 receptor expression upon T cell receptor activation. Here, we demonstrate that basal Notch-1 expression is decreased in T cells from active SLE patients at the mRNA and protein levels in various T cell subpopulations. Notch-1 transcript numbers inversely correlate with disease activity in SLE patients. We provide evidence that both enhanced histone H3 methylation and CpG DNA methylation of the human Notch-1 promoter contribute to decreased Notch-1 expression in SLE T cells. Previous data from our group identified cAMP-responsive element modulator α (CREMα), which is up-regulated in SLE T cells, as a key regulator of epigenetic patterns and gene transcription, e.g. that of IL2 and IL17 genes. In this study, we observed increased CREMα binding to the Notch-1 promoter, which eventually resulted in significantly reduced Notch-1 promoter activity and gene transcription. Notably, decreased Notch-1 levels were associated with elevated IL-17A levels. Our data suggest a role for Notch-1 in SLE immunopathogenesis, and for the first time, we present molecular mechanisms that mediate dysregulated Notch-1 expression in SLE T cells.
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Registered trials
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