ArticleProceedings of the National Academy of Sciences of the United States of America2012
cAMP response element modulator α controls IL2 and IL17A expression during CD4 lineage commitment and subset distribution in lupus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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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.
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
63 citing papers in PubMed, 108 citations in OpenAlex.
- CaMK4-dependent activation of AKT/mTOR and CREM-α underlies autoimmunity-associated Th17 imbalance.The Journal of clinical investigation · 2014Trial
- cAMP responsive element modulator (CREM) α mediates chromatin remodeling of CD8 during the generation of CD3+ CD4- CD8- T cells.The Journal of biological chemistry · 2014Trial
- cAMP-responsive element modulator α (CREMα) trans-represses the transmembrane glycoprotein CD8 and contributes to the generation of CD3+CD4-CD8- T cells in health and disease.The Journal of biological chemistry · 2013Trial
- An Update Comprehensive Review on Epigenetic Modifications and Therapies in Autoimmune Diseases.Clinical reviews in allergy & immunology · 2026Review
- Unveiling Molecular Mechanisms Underlying Obesity-Associated Systemic Lupus Erythematosus.Endocrinology, diabetes & metabolism · 2025Review
- Automated high-throughput profiling of single-cell total transcriptome with scComplete-seq.Nucleic acids research · 2025Article
- Genome-Wide Impact of Folic Acid on DNA Methylation and Gene Expression in Lupus Adipocytes: An In Vitro Study on Obesity.Nutrients · 2025Article
- Gluconolactone restores immune regulation and alleviates skin inflammation in lupus-prone mice and in patients with cutaneous lupus.Science translational medicine · 2025Article
- Protein phosphatases in systemic autoimmunity.Immunometabolism (Cobham, Surrey) · 2025Review
- SIT1 identifies circulating hypoactive T cells with elevated cytotoxic molecule secretion in systemic lupus erythematosus patients.Immunologic research · 2024Article
- Epigenetic control of adaptive or homeostatic splicing during interval-training activities.Nucleic acids research · 2024Article
- Methylation of T and B Lymphocytes in Autoimmune Rheumatic Diseases.Clinical reviews in allergy & immunology · 2024Review
- Helios as a Potential Biomarker in Systemic Lupus Erythematosus and New Therapies Based on Immunosuppressive Cells.International journal of molecular sciences · 2023Review
- Novel Aspects of cAMP-Response Element Modulator (CREM) Role in Spermatogenesis and Male Fertility.International journal of molecular sciences · 2023Review
- Endosome Traffic Modulates Pro-Inflammatory Signal Transduction in CD4International journal of molecular sciences · 2023Review
- The star target in SLE: IL-17.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Decreased SUV39H1 at the promoter region leads to increased CREMα and accelerates autoimmune response in CD4Clinical epigenetics · 2022Article
- Role of Glutaminase 2 in Promoting CD4+ T Cell Production of Interleukin-2 by Supporting Antioxidant Defense in Systemic Lupus Erythematosus.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- The deacetylase SIRT2 contributes to autoimmune disease pathogenesis by modulating IL-17A and IL-2 transcription.Cellular & molecular immunology · 2022Article
- Heterogeneity and clonality of kidney-infiltrating T cells in murine lupus nephritis.JCI insight · 2022Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Appropriate expression of IL-2 plays a central role during the priming and differentiation of T cells. A tight balance between IL-2 and the effector cytokine IL-17A is essential for immune homeostasis. Epigenetic mechanisms have been documented as a key component of cytokine regulation during lineage commitment. The molecular mechanisms that induce chromatin remodeling are less well understood. We investigated epigenetic regulators that mediate the diametric expression of IL-2 and IL-17A in naive, central memory, and effector memory CD4(+) T cells. We demonstrate that cAMP response modulator (CREM)α contributes to epigenetic remodeling of IL2 in effector memory T cells through the recruitment of DNMT3a. CREMα also reduces CpG-DNA methylation of the IL17A promoter. CREMα expression is regulated at the epigenetic level by CpG-DNA methylation, which allows increased CREMα expression in effector memory CD4(+) T cells. T cells from patients with systemic lupus erythematosus (SLE) express increased levels of CREMα and exhibit a phenotype that is similar to effector memory CD4(+) T cells with epigenetically predetermined expression patterns of IL-2 and IL-17A. We conclude that CREMα mediates epigenetic remodeling of the IL2 and IL17A gene during T-cell differentiation in favor of effector memory T cells in health and disease.
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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.