IL-2 is a key cytokine during proliferation and activation of T lymphocytes and 
functions as an auto- and paracrine growth factor. Regardless of activating 
effects on T lymphocytes, the absence of IL-2 has been linked to the development 
of autoimmune pathology in mice and humans. Systemic lupus erythematosus (SLE) 
is a multifactorial autoimmune disease and characterized by dysregulation of 
lymphocyte function, transcription factor and cytokine expression, and antigen 
presentation. Reduced IL-2 expression is a hallmark of SLE T lymphocytes and 
results in decreased numbers of regulatory T lymphocytes which play an important 
role in preventing autoimmunity. Reduced IL-2 expression was linked to 
overproduction of the transcription regulatory factor cAMP-responsive element 
modulator (CREM)α in SLE T lymphocytes and subsequent CREMα binding to a CRE 
site within the IL2 promoter (-180 CRE). In this study, we demonstrate the 
involvement of CREMα-mediated IL2 silencing in T lymphocytes from SLE patients 
through a gene-wide histone deacetylase 1-directed deacetylation of histone 
H3K18 and DNA methyltransferase 3a-directed cytosine phosphate guanosine 
(CpG)-DNA hypermethylation. For the first time, we provide direct evidence that 
CREMα mediates silencing of the IL2 gene in SLE T cells though histone 
deacetylation and CpG-DNA methylation.