cAMP responsive element modulator: a critical regulator of cytokine production

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 alpha (CREM alpha). Recent evidence indicates that CREM alpha 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 CREM alpha as a key molecule that drives autoimmunity.