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Publisher DOI: 10.1038/msb.2012.56
Title: PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells
Language: English
Authors: He, Feng 
Chen, Hairong 
Probst-Kepper, Michael 
Geffers, Robert 
Eifes, Serge 
Sol, Antonio del 
Schughart, Klaus 
Zeng, An-Ping  
Balling, Rudi 
Keywords: high time-resolution time series;human CD4 regulatory T cell;infer key genes from undirected gene networks;Plau knockout mice;Treg development and suppressor function
Issue Date: 20-Nov-2012
Publisher: EMBO ; Macmillan Publishers
Source: Molecular systems biology (8): art. no. 624 (2012)
Journal or Series Name: Molecular systems biology 
Abstract (english): Human FOXP3(+)CD25(+)CD4(+) regulatory T cells (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.
DOI: 10.15480/882.1930
ISSN: 1744-4292
Institute: Bioprozess- und Biosystemtechnik V-1 
Type: (wissenschaftlicher) Artikel
License: CC BY-NC-SA 3.0 (Attribution-NonCommercial-ShareAlike) CC BY-NC-SA 3.0 (Attribution-NonCommercial-ShareAlike)
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