{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hedrich CM"],"funding":["NIAID NIH HHS","NIAMS NIH HHS"],"pagination":["16606-11"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3478624"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["109(41)"],"pubmed_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."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["cAMP response element modulator α controls IL2 and IL17A expression during CD4 lineage commitment and subset distribution in lupus."],"pmcid":["PMC3478624"],"funding_grant_id":["R01 AI085567","R01 AI049954","R01 AI42269","R01 AI042269","R01 AR060849","R37 AI049954","R01 AI49954","R01 AI85567"],"pubmed_authors":["Lo MS","Hedrich CM","Rauen T","Kyttaris VC","Ioannidis C","Tsokos GC","Apostolidis SA","Crispin JC"],"additional_accession":[]},"is_claimable":false,"name":"cAMP response element modulator α controls IL2 and IL17A expression during CD4 lineage commitment and subset distribution in lupus.","description":"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.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Oct","modification":"2024-11-07T14:17:02.969Z","creation":"2019-03-27T00:59:23Z"},"accession":"S-EPMC3478624","cross_references":{"pubmed":["23019580"],"doi":["10.1073/pnas.1210129109"]}}