title: 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.affiliation: From the Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Hedrich
authors.forename: Thomas
authors.initials: T
authors.lastname: Rauen
authors.forename: Jose C
authors.initials: JC
authors.lastname: Crispin
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Koga
authors.forename: Christina
authors.initials: C
authors.lastname: Ioannidis
authors.forename: Melissa
authors.initials: M
authors.lastname: Zajdel
authors.forename: Vasileios C
authors.initials: VC
authors.lastname: Kyttaris
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D017252:CD3 Complex / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020218:Response Elements; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; C477867:CD8beta antigen; C497410:CREM protein, human; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator
keywords: Autoimmune Diseases; CD8; CREMα; Cell Differentiation; Cellular Immune Response; Double-negative T Cells; Gene Regulation; SLE; T Cell
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