of the IL17 gene into an open, accessible state, which allows additional transcription factors to bind. The exact mechanisms by which CREMα mediate histone acetylation in this region while mediating diametric histone modification around the IL2 gene remains to be elucidated. However, the ‘transcription factor environment’ of the two promoters may affect this process. At the transcriptional level, CREMα mediates differential effects on the IL17A (trans-activation) and the IL17F (trans-repression) promoters, which ultimately results in increased IL17A and decreased IL17F mRNA expression and protein levels in SLE patients. Although CREMα confers an activating, open pattern to the IL17F gene in SLE T cells, its repressive functions on the IL17F promoter prevail and dictate the ultimately decreased IL-17F production in these cells. The imbalanced IL-17A/IL-17F ratio in activated T cells, which may largely be attributed to the CREMα effects described above, appears to be specific for SLE T cells because T cells from healthy individuals and patients with other autoimmune diseases do not necessarily upregulate IL-17A and downregulate IL-17F production upon activation [46]. Notably, the observed effects of CREMα on IL-2 and IL-17A cytokine production in humans are also observed in transgenic mice with T cell-specific CREMα overexpression (under control of
