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.

Abstract	T cell receptor-αβ(+) CD3(+)CD4(-)CD8(-) "double-negative" T cells are expanded in the peripheral blood of patients with systemic lupus erythematosus and autoimmune lymphoproliferative syndrome. In both disorders, double-negative T cells infiltrate tissues, induce immunoglobulin production, and secrete proinflammatory cytokines. Double-negative T cells derive from CD8(+) T cells through down-regulation of CD8 surface co-receptors. However, the molecular mechanisms orchestrating this process remain unclear. Here, we demonstrate that the transcription factor cAMP-responsive element modulator α (CREMα), which is expressed at increased levels in T cells from systemic lupus erythematosus patients, contributes to transcriptional silencing of CD8A and CD8B. We provide the first evidence that CREMα trans-represses a regulatory element 5' of the CD8B gene. Therefore, CREMα represents a promising candidate in the search for biomarkers and treatment options in diseases in which double-negative T cells contribute to the pathogenesis.
Authors	Christian M Hedrich, Thomas Rauen, Jose C Crispin, Tomohiro Koga, Christina Ioannidis, Melissa Zajdel, Vasileios C Kyttaris, George C Tsokos
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 288 Issue 44 Pg. 31880-7 (Nov 01 2013) ISSN: 1083-351X [Electronic] United States
PMID	24047902 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural)
Chemical References	CD3 Complex CD4 Antigens CD8 Antigens CD8 antigen, alpha chain CD8beta antigen CREM protein, human Repressor Proteins Cyclic AMP Response Element Modulator
Topics	CD3 Complex (genetics, immunology, metabolism) CD4 Antigens (genetics, immunology, metabolism) CD8 Antigens (biosynthesis, genetics, immunology) CD8-Positive T-Lymphocytes (immunology, metabolism, pathology) Cyclic AMP Response Element Modulator (genetics, immunology, metabolism) Female Gene Silencing Humans Lupus Erythematosus, Systemic (genetics, immunology, metabolism, pathology) Male Repressor Proteins (genetics, immunology, metabolism) Response Elements Transcription, Genetic (genetics, immunology)

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