Walters Emily, Rider Virginia, Abdou Nabih I, Greenwell Cindy, Svojanovsky Stan, Smith Peter, Kimler Bruce F
Department of Biology, Pittsburg State University, Pittsburg, KS 66762, USA.
Clin Immunol. 2009 Dec;133(3):428-36. doi: 10.1016/j.clim.2009.09.002. Epub 2009 Sep 30.
The major risk factor for developing systemic lupus erythematosus (SLE) is being female. The present study utilized gene profiles of activated T cells from females with SLE and healthy controls to identify signaling pathways uniquely regulated by estradiol that could contribute to SLE pathogenesis. Selected downstream pathway genes (+/- estradiol) were measured by real time polymerase chain amplification. Estradiol uniquely upregulated six pathways in SLE T cells that control T cell function including interferon-alpha signaling. Measurement of interferon-alpha pathway target gene expression revealed significant differences (p= 0.043) in DRIP150 (+/- estradiol) in SLE T cell samples while IFIT1 expression was bimodal and correlated moderately (r= 0.55) with disease activity. The results indicate that estradiol alters signaling pathways in activated SLE T cells that control T cell function. Differential expression of transcriptional coactivators could influence estrogen-dependent gene regulation in T cell signaling and contribute to SLE onset and disease pathogenesis.
患系统性红斑狼疮（SLE）的主要风险因素是女性。本研究利用来自SLE女性患者和健康对照的活化T细胞的基因谱，来鉴定由雌二醇独特调控的、可能导致SLE发病机制的信号通路。通过实时聚合酶链扩增来测量选定的下游通路基因（有无雌二醇）。雌二醇在SLE T细胞中独特地上调了六条控制T细胞功能的通路，包括α-干扰素信号通路。对α-干扰素通路靶基因表达的测量显示，SLE T细胞样本中DRIP150（有无雌二醇）存在显著差异（p = 0.043），而IFIT1表达呈双峰，且与疾病活动度中度相关（r = 0.55）。结果表明，雌二醇改变了活化的SLE T细胞中控制T细胞功能的信号通路。转录共激活因子的差异表达可能影响T细胞信号传导中雌激素依赖性基因调控，并促成SLE的发病和疾病发病机制。
