[HTML][HTML] Systemic lupus erythematosus serum IgG increases CREM binding to the IL-2 promoter and suppresses IL-2 production through CaMKIV

YT Juang, Y Wang, EE Solomou, Y Li… - The Journal of …, 2005 - Am Soc Clin Investig
YT Juang, Y Wang, EE Solomou, Y Li, C Mawrin, K Tenbrock, VC Kyttaris, GC Tsokos
The Journal of clinical investigation, 2005Am Soc Clin Investig
Systemic lupus erythematosus (SLE) T cells express high levels of cAMP response element
modulator (CREM) that binds to the IL-2 promoter and represses the transcription of the IL-2
gene. This study was designed to identify pathways that lead to increased binding of CREM
to the IL-2 promoter in SLE T cells. Ca 2+/calmodulin–dependent kinase IV (CaMKIV) was
found to be increased in the nucleus of SLE T cells and to be involved in the overexpression
of CREM and its binding to the IL-2 promoter. Treatment of normal T cells with SLE serum …
Systemic lupus erythematosus (SLE) T cells express high levels of cAMP response element modulator (CREM) that binds to the IL-2 promoter and represses the transcription of the IL-2 gene. This study was designed to identify pathways that lead to increased binding of CREM to the IL-2 promoter in SLE T cells. Ca 2+/calmodulin–dependent kinase IV (CaMKIV) was found to be increased in the nucleus of SLE T cells and to be involved in the overexpression of CREM and its binding to the IL-2 promoter. Treatment of normal T cells with SLE serum resulted in increased expression of CREM protein, increased binding of CREM to the IL-2 promoter, and decreased IL-2 promoter activity and IL-2 production. This process was abolished when a dominant inactive form of CaMKIV was expressed in normal T cells. The effect of SLE serum resided within the IgG fraction and was specifically attributed to anti–TCR/CD3 autoantibodies. This study identifies CaMKIV as being responsible for the increased expression of CREM and the decreased production of IL-2 in SLE T cells and demonstrates that anti–TCR/CD3 antibodies present in SLE sera can account for the increased expression of CREM and the suppression of IL-2 production.
The Journal of Clinical Investigation