T lymphocytes from patients with systemic lupus erythematosus (SLE) display a complex array of cellular, molecular, and signaling anomalies, many of which have been attributed to increased expression of the transcriptional regulator cAMP responsive element modulator α (CREMα). Recent evidence indicates that CREMα, in addition to its regulatory functions on gene promoters in T lymphocytes, alters the epigenetic conformation of cytokine genes by interacting with enzymes that control histone methylation and acetylation as well as cytosine-phosphate-guanosine (CpG) DNA methylation. This review summarizes the most recent findings on CREM protein expression in various cell types, in particular its effects on T lymphocyte biology in the context of both health and SLE. We emphasize CREMα as a key molecule that drives autoimmunity.
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