NOTCH1 and systemic lupus erythematosus: Previous studies have demonstrated that the downregulation of IL-2 [35, 67, 71], IL-17 [66], and Notch-1 [69] in SLE T lymphocytes was due to the binding cAMP-responsive element modulator (CREM)-α to the promoter of the genes followed by enhanced CpG DNA methylation.