Kyttaris Vasileios C, Wang Ying, Juang Yuang-Taung, Weinstein Arthur, Tsokos George C
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
J Immunol. 2007 Feb 1;178(3):1960-6. doi: 10.4049/jimmunol.178.3.1960.
T cells from patients with systemic lupus erythematosus (SLE) are characterized by heightened TCR-initiated free intracytoplasmic calcium responses. We demonstrate that activated T cells from SLE patients, but not from rheumatoid arthritis patients, displayed higher levels of the calcineurin-dependent transcription factor NF-ATc2 in the nucleus compared with control T cells. DNA NF-AT-binding activity was also increased, as was the amount of NF-ATc2 bound to the promoters of CD154 (CD40L) and IL-2 genes. Nevertheless, although high NF-ATc2 levels translated into higher CD154 transcription in SLE, IL-2 transcription was decreased. The absence of important transcriptional activators (AP-1, NF-kappaBeta) and the presence of transcriptional repressors (cAMP response element modulator) on the IL-2 promoter explain this dichotomous effect.
系统性红斑狼疮（SLE）患者的T细胞具有TCR启动的胞浆内游离钙反应增强的特征。我们证明，与对照T细胞相比，来自SLE患者而非类风湿性关节炎患者的活化T细胞核内钙调神经磷酸酶依赖性转录因子NF-ATc2水平更高。DNA的NF-AT结合活性也增加，与CD154（CD40L）和IL-2基因启动子结合的NF-ATc2量也增加。然而，尽管SLE中高NF-ATc2水平转化为更高的CD154转录，但IL-2转录却下降。IL-2启动子上重要转录激活因子（AP-1、NF-κB）的缺失和转录抑制因子（cAMP反应元件调节剂）的存在解释了这种二分效应。
