Expression and function of Cbl-b in T cells from patients with systemic lupus erythematosus, and detection of the 2126 A/G Cblb gene polymorphism in the Mexican mestizo population
Expression and function of Cbl-b in T cells from patients with systemic lupus erythematosus, and detection of the 2126 A/G Cblb gene polymorphism in the Mexican mestizo population
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DOI：
10.1177/0961203310394896
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发表时间：
2011-05-01
期刊：
影响因子：
2.6
通讯作者：
Baranda-Candido, L.
中科院分区：
文献类型：
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作者：
Doniz-Padilla, L.;Martinez-Jimenez, V.;Baranda-Candido, L.
系统性红斑狼疮(SLE)是以T、B淋巴细胞功能异常及其受体诱导的信号通路异常为特征的疾病。CBL-b是一种细胞内适配子蛋白，在淋巴细胞活性的负性调节中起关键作用。我们探讨了Cbl-b在SLE患者T淋巴细胞中的表达和功能。此外，还确定了SLE与Cblb基因的单核苷酸多态(SNP)的可能关联。我们研究了150名SLE患者、163名健康人和14名类风湿关节炎(RA)患者。分析Cbl-b在外周血单个核细胞中的表达，并通过分析CD3诱导的肌动蛋白聚合和JNK、c-Jun的磷酸化来评价Cbl-b的负性调节功能。用实时定量聚合酶链式反应检测Cblb基因的2126(A/G)SNP。我们发现，与健康对照组或RA患者相比，SLE患者T淋巴细胞中Cbl-b的表达显著降低，c-jun和肌动蛋白聚合的活化水平增加。此外，2126(A/G)SNP与系统性红斑狼疮显著相关。我们的数据表明，Cbl-b可能参与了SLE患者T淋巴细胞的非调节激活。狼疮(2011)20,628-635。
Systemic lupus erythematosus (SLE) is characterized by abnormalities in the function of T and B lymphocytes and in the signaling pathways induced through their receptors. Cbl-b is an intracellular adaptor protein that plays a key role in the negative regulation of lymphocyte activity. We explored the expression and function of Cbl-b in T lymphocytes from SLE patients. In addition, the possible association of SLE and a single nucleotide polymorphism (SNP) of the Cblb gene was determined. We studied 150 SLE patients, 163 healthy individuals, and 14 patients with rheumatoid arthritis (RA). The expression of Cbl-b was analyzed in the peripheral blood mononuclear cells, and the negative regulatory function of Cbl-b was assessed by analyzing actin polymerization and the phosphorylation of JNK and c-Jun induced through CD3. Furthermore, the 2126(A/G) SNP of the Cblb gene was detected by real-time polymerase chain reaction. We found a significant small reduction in the expression of Cbl-b as well as increased levels of activation of c-Jun and actin polymerization in T lymphocytes from patients with SLE compared with healthy controls or RA patients. In addition, a significant association between the 2126(A/G) SNP and SLE was detected. Our data suggest that Cbl-b may contribute to the deregulated activation of T lymphocytes observed in SLE. Lupus (2011) 20, 628-635.