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- Title
Systemic lupus erythematosus serum lgG increases CREM binding to the IL-2 promoter and suppresses IL-2 production through CaMKIV.
- Authors
Juang, Yuang-Taung; Wang, Ying; Solomou, Elena E.; Li, Yansong; Mawrin, Christian; Tenbrock, Klaus; Kyttaris, Vasileios C.; Tsokos, George C.
- Abstract
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. Ca2+/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.
- Subjects
LUPUS erythematosus; IMMUNOGLOBULIN G; T cells; INTERLEUKIN-2; CALMODULIN; PROTEINS
- Publication
Journal of Clinical Investigation, 2005, Vol 115, Issue 4, p996
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI200522854