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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Varying expression of four genes sharing a common regulatory sequence may differentiate rheumatoid arthritis from ageing effects on the CD4(+) lymphocytes.
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Varying expression of four genes sharing a common regulatory sequence may differentiate rheumatoid arthritis from ageing effects on the CD4(+) lymphocytes.

机译：共有共同调控序列的四个基因的变化表达可能将类风湿性关节炎与CD4（+）淋巴细胞的衰老效应区分开。

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摘要

The CD28 gene is similarly down-regulated in CD4(+) lymphocytes from both healthy elderly people and patients with rheumatoid arthritis (RA) because of impaired protein-binding activity of the 'alpha' sequence in its promoter region. Other genes important for the CD4(+) cell function may share that sequence and may be similarly regulated and affected. We searched GenBank for possible 'alpha' homologues and then compared transcriptional activities of the respective genes in the CD4(+) cells of young and older healthy individuals and those with RA by real-time PCR. We show here that genes encoding one of the zinc finger proteins (ZNF334), the 'aging hormone' Klotho, the retinoid acid receptor beta2 (RARbeta2) and the T-cell adapter protein GRAP-2, contain sequences with various (exceeding 70%) degrees of homology to the 'alpha' sequence near their promoters. These genes are transcribed in human CD4(+) lymphocytes; the expressions of RARbeta2, KLOTHO and ZNF334 are significantly decreased in a correlated manner in the cells of patients with RA compared with those of healthy individuals. In RA patients, the extremely reduced expression of ZNF334 does not depend on the individual's age, apparently constituting a disease-related phenomenon; whereas that of RARbeta2 and KLOTHO occurs mostly in the cells of relatively younger patients, making them similar to the lymphocytes of healthy elderly in this aspect.
机译：由于健康的老年人和类风湿性关节炎（RA）患者的CD4（+）淋巴细胞中的CD28基因类似地下调，因为其启动子区域中“α”序列的蛋白结合活性受损。其他对CD4（+）细胞功能重要的基因可能共享该序列，并且可能受到类似的调节和影响。我们在GenBank中搜索了可能的“ alpha”同源物，然后通过实时PCR比较了年轻和年长健康个体以及RA患者的CD4（+）细胞中各个基因的转录活性。我们在这里显示，编码锌指蛋白（ZNF334），“衰老激素” Klotho，类维生素A受体β2（RARbeta2）和T细胞衔接子蛋白GRAP-2的基因所包含的序列具有各种序列（超过70％ ）与启动子附近的“ alpha”序列的同源性。这些基因在人类CD4（+）淋巴细胞中转录;与健康个体相比，RA患者细胞中RARbeta2，KLOTHO和ZNF334的表达显着降低。在RA患者中，ZNF334的极度降低并不取决于个体的年龄，这显然构成了与疾病相关的现象。而RARbeta2和KLOTHO的细胞大多发生在相对年轻的患者的细胞中，这使得它们与健康老年人的淋巴细胞相似。

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