Work

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

Year: 2013

Type: article

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. Background: Expanded CD3 + CD4 − CD8 − T cells in SLE originate from CD8 + T cells. Results: CREMα trans -represses CD8 gene transcription. Conclusion: By trans -repressing CD8 expression, CREMα contributes to double-negative T cell expansion in SLE pathogenesis. Significance: CREMα modulates T cell subset distribution and cytokine expression.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m113.508655