Pfoertner Susanne, Jeron Andreas, Probst-Kepper Michael, Guzman Carlos A, Hansen Wiebke, Westendorf Astrid M, Toepfer Tanja, Schrader Andres J, Franzke Anke, Buer Jan, Geffers Robert
Department of Mucosal Immunity, German Research Centre for Biotechnology, Braunschweig, Germany.
Genome Biol. 2006;7(7):R54. doi: 10.1186/gb-2006-7-7-r54.
Naturally occurring CD4+ CD25+ regulatory T cells (TReg) are involved in the control of autoimmune diseases, transplantation tolerance, and anti-tumor immunity. Thus far, genomic studies on TReg cells were restricted to murine systems, and requirements for their development, maintenance, and mode of action in humans are poorly defined.
To improve characterization of human TReg cells, we compiled a unique microarray consisting of 350 TReg cell associated genes (Human TReg Chip) based on whole genome transcription data from human and mouse TReg cells. TReg cell specific gene signatures were created from 11 individual healthy donors. Statistical analysis identified 62 genes differentially expressed in TReg cells, emphasizing some cross-species differences between mice and humans. Among them, several 'old friends' (including FOXP3, CTLA4, and CCR7) that are known to be involved in TReg cell function were recovered. Strikingly, the vast majority of genes identified had not previously been associated with human TReg cells (including LGALS3, TIAF1, and TRAF1). Most of these 'new players' however, have been described in the pathogenesis of autoimmunity. Real-time RT-PCR of selected genes validated our microarray results. Pathway analysis was applied to extract signaling modules underlying human TReg cell function.
The comprehensive set of genes reported here provides a defined starting point to unravel the unique characteristics of human TReg cells. The Human TReg Chip constructed and validated here is available to the scientific community and is a useful tool with which to study the molecular mechanisms that orchestrate TReg cells under physiologic and diseased conditions.
天然存在的CD4+ CD25+调节性T细胞（TReg）参与自身免疫性疾病、移植耐受和抗肿瘤免疫的调控。迄今为止，关于TReg细胞的基因组研究仅限于小鼠系统，其在人类中的发育、维持及作用模式仍不清楚。
为了更好地表征人类TReg细胞，我们基于人和小鼠TReg细胞的全基因组转录数据，编制了一个由350个TReg细胞相关基因组成的独特微阵列（人类TReg芯片）。从11名健康个体供体中创建了TReg细胞特异性基因特征。统计分析确定了62个在TReg细胞中差异表达的基因，突出了小鼠和人类之间的一些种间差异。其中，回收了几个已知参与TReg细胞功能的“老朋友”（包括FOXP3、CTLA4和CCR7）。引人注目的是，鉴定出的绝大多数基因以前未与人类TReg细胞相关联（包括LGALS3、TIAF1和TRAF1）。然而，这些“新成员”中的大多数已在自身免疫性疾病的发病机制中被描述。对选定基因进行实时RT-PCR验证了我们的微阵列结果。应用通路分析提取人类TReg细胞功能的潜在信号模块。
本文报道的这组全面的基因提供了一个明确的起点，以揭示人类TReg细胞的独特特征。这里构建并验证的人类TReg芯片可供科学界使用，是研究在生理和疾病条件下协调TReg细胞的分子机制的有用工具。
