Department of Biology, Pittsburg State University, Pittsburg, Kansas 66762, USA.
Lupus. 2013 May;22(6):583-96. doi: 10.1177/0961203313482742. Epub 2013 Mar 27.
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects women nine times more often than men. The present study investigates estradiol-dependent control of the calcium-buffering protein, calreticulin, to gain further insight into the molecular basis of abnormal T cell signaling in SLE T cells.
T cells were purified from blood samples obtained from healthy females and SLE patients. Calreticulin expression was quantified by real-time polymerase chain amplification. Calreticulin and estrogen receptor-α were co-precipitated and analyzed by Western blotting to determine if the proteins associate in T cells.
Calreticulin expression increased (p = 0.034) in activated control T cells, while estradiol decreased (p = 0.044) calreticulin in resting T cells. Calreticulin expression decreased in activated SLE T cell samples and increased in approximately 50% of resting T cell samples. Plasma estradiol was similar (p > 0.05) among SLE patients and control volunteers. Estrogen receptor-α and calreticulin co-precipitated from nuclear and cytoplasmic T cell compartments.
The results indicate that estradiol tightly regulates calreticulin expression in normal human T cells, and the dynamics are different between activated and resting T cells. The absence of this tight regulation in SLE T cells could contribute to abnormal T cell function.
红斑狼疮（SLE）是一种自身免疫性疾病，女性患病的几率是男性的九倍。本研究旨在探讨雌二醇对钙缓冲蛋白钙网蛋白的依赖性调控，以期深入了解 SLE T 细胞中异常 T 细胞信号转导的分子基础。
从健康女性和 SLE 患者的血液样本中纯化 T 细胞。采用实时聚合酶链扩增法定量检测钙网蛋白的表达。用 Western blot 分析钙网蛋白和雌激素受体-α共沉淀，以确定这两种蛋白是否在 T 细胞中相互作用。
在激活的对照 T 细胞中，钙网蛋白表达增加（p=0.034），而雌二醇则降低了静息 T 细胞中的钙网蛋白（p=0.044）。在激活的 SLE T 细胞样本中，钙网蛋白表达降低，而在大约 50%的静息 T 细胞样本中，钙网蛋白表达增加。SLE 患者和对照组志愿者的血浆雌二醇水平相似（p>0.05）。雌激素受体-α和钙网蛋白从 T 细胞的核和细胞质部分共沉淀。
结果表明，雌二醇在正常人类 T 细胞中对钙网蛋白的表达进行严格调控，而在激活和静息 T 细胞中，这种调控的动态是不同的。SLE T 细胞中缺乏这种严格的调控可能导致异常的 T 细胞功能。
