Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2013 Aug 27;8(8):e74550. doi: 10.1371/journal.pone.0074550. eCollection 2013.
Engagement of the CD3/T cell receptor complex in systemic lupus erythematosus (SLE) T cells involves Syk rather than the zeta-associated protein. Because Syk is being considered as a therapeutic target we asked whether Syk is central to the multiple aberrantly modulated molecules in SLE T cells. Using a gene expression array, we demonstrate that forced expression of Syk in normal T cells reproduces most of the aberrantly expressed molecules whereas silencing of Syk in SLE T cells normalizes the expression of most abnormally expressed molecules. Protein along with gene expression modulation for select molecules was confirmed. Specifically, levels of cytokine IL-21, cell surface receptor CD44, and intracellular molecules PP2A and OAS2 increased following Syk overexpression in normal T cells and decreased after Syk silencing in SLE T cells. Our results demonstrate that levels of Syk affect the expression of a number of enzymes, cytokines and receptors that play a key role in the development of disease pathogenesis in SLE and provide support for therapeutic targeting in SLE patients.
系统性红斑狼疮（SLE）T 细胞中 CD3/T 细胞受体复合物的结合涉及 Syk 而不是 ζ 相关蛋白。由于 Syk 被认为是一个治疗靶点，我们想知道 Syk 是否是 SLE T 细胞中多个异常调节分子的核心。我们使用基因表达阵列表明，在正常 T 细胞中强制表达 Syk 可再现大多数异常表达的分子，而在 SLE T 细胞中沉默 Syk 可使大多数异常表达的分子的表达正常化。我们还证实了特定分子的蛋白质和基因表达调节。具体而言，在正常 T 细胞中过表达 Syk 后，细胞因子 IL-21、细胞表面受体 CD44 和细胞内分子 PP2A 和 OAS2 的水平增加，而在 SLE T 细胞中沉默 Syk 后，这些分子的水平降低。我们的结果表明，Syk 的水平影响许多在 SLE 发病机制中起关键作用的酶、细胞因子和受体的表达，并为 SLE 患者的治疗靶向提供支持。
