PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells
PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells
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DOI：
10.1038/msb.2012.56
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发表时间：
2012-11-01
影响因子：
9.9
通讯作者：
Balling, Rudi
中科院分区：
文献类型：
--
作者：
He, Feng;Chen, Hairong;Balling, Rudi
人FOXP 3（+）CD 25（+）CD 4（+）调节性T细胞（Tcells，Tcells）是维持免疫稳态所必需的。已知几个基因对鼠THBE是重要的，但是对于人THBE，控制抑制功能的基因和潜在的分子网络仍然在很大程度上不清楚。在这里，我们描述了一种直接从无向相关网络中识别关键基因的策略，该网络是我们在人Tcl 3/CD 4（+）T效应细胞活化期间从非常高的时间分辨率（HTR）转录组重建的。我们表明，预测排名第一的新的关键基因PLAU（纤溶酶原激活剂尿激酶）是重要的抑制功能的人类和小鼠THBG。进一步的分析揭示了PLAU对记忆性T细胞调节特别重要，并且PLAU通过STAT 5和ERK信号通路介导Treg抑制剂功能。我们的研究表明，使用基于HTR数据的网络策略，有可能为复杂的动态生物过程确定新的关键基因，并揭示了PLAU在Treg抑制功能中的关键作用。Molecular Systems Biology 8：624; 2012年11月20日在线发表; doi：10.1038/msb.2012.56
Human FOXP3(+)CD25(+)CD4(+) regulatory Tcells (Tregs) are essential to the maintenance of immune homeostasis. Several genes are known to be important for murine Tregs, but for human Tregs the genes and underlying molecular networks controlling the suppressor function still largely remain unclear. Here, we describe a strategy to identify the key genes directly from an undirected correlation network which we reconstruct from a very high time-resolution (HTR) transcriptome during the activation of human Tregs/CD4(+) T-effector cells. We show that a predicted top-ranked new key gene PLAU (the plasminogen activator urokinase) is important for the suppressor function of both human and murine Tregs. Further analysis unveils that PLAU is particularly important for memory Tregs and that PLAU mediates Treg suppressor function via STAT5 and ERK signaling pathways. Our study demonstrates the potential for identifying novel key genes for complex dynamic biological processes using a network strategy based on HTR data, and reveals a critical role for PLAU in Treg suppressor function. Molecular Systems Biology 8:624; published online 20 November 2012; doi:10.1038/msb.2012.56