Transcript imaging of the development of human T helper cells using oligonucleotide arrays
Transcript imaging of the development of human T helper cells using oligonucleotide arrays
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DOI：
10.1038/75671
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发表时间：
2000-05-01
期刊：
影响因子：
30.8
通讯作者：
Certa, U
中科院分区：
文献类型：
--
作者：
Rogge, L;Bianchi, E;Certa, U
许多病理过程，包括引起过敏和自身免疫性疾病的病理过程，都与炎症部位存在特殊的辅助性 T 细胞亚群有关(1) 了解控制 1 型辅助性 T (Th1) 与 2 型辅助性 T (Th2) 细胞功能特性的遗传程序可能有助于深入了解炎症性疾病的病理生理学。我们使用高密度寡核苷酸阵列比较了人类 Th1 和 Th2 细胞的基因表达谱，该阵列能够显示 6,000 个人类基因的转录水平。在这里，我们使用统计算法分析来自五个独立实验的数据集。该方法鉴定了 215 个差异表达基因，编码参与转录调控、细胞凋亡、蛋白水解以及细胞粘附和迁移的蛋白质。通过动力学 PCR 分析证实，通过将分化的 Th1 细胞暴露于白细胞介素 12 (IL-12)，这些基因的 A 子集进一步上调，表明 IL-12 在没有抗原刺激的情况下调节 Th1 细胞的效应器功能。所选基因的功能测定和体内表达验证了我们研究的生物学相关性。我们的结果为控制 T 辅助细胞亚群功能多样性的转录程序提供了新的见解。
Many pathological processes, including those causing allergies and autoimmune diseases, are associated with the presence of specialized subsets of T helper cells at the site of inflammation(1) Understanding the genetic program that controls the functional properties of T helper type 1 (Th1) versus T helper type 2 (Th2) cells may provide insight into the pathophysiology of inflammatory diseases. We compared the gene-expression profiles of human Th1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6,000 human genes'. Here we analyse the data sets derived from five independent experiments using statistical algorithms. This approach resulted in the identification of 215 differentially expressed genes, encoding proteins involved in transcriptional regulation, apoptosis, proteolysis, and cell adhesion and migration. A-subset of these genes was further upregulated by exposure of differentiated Th1 cells to interleukin-12 (IL-12), as confirmed by kinetic PCR analysis, indicating that IL-12 modulates the effector functions of Th1 cells in the absence of antigenic stimulation. Functional assays and in vivo expression of selected genes have validated the biological relevance of our study. Our results provide new insight into the transcriptional program controlling the functional diversity of subsets of T helper cells.