PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells.
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Authors
He, FengChen, Hairong
Probst-Kepper, Michael
Geffers, Robert
Eifes, Serge
Del Sol, Antonio
Schughart, Klaus
Zeng, An-Ping
Balling, Rudi
Issue Date
2012-11-20
Metadata
Show full item recordAbstract
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.Citation
PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells. 2012, 8:624 Mol. Syst. Biol.Affiliation
1] Department of Infection Genetics, Helmholtz Centre for Infection Research (HZI), University of Veterinary Medicine Hannover, Braunschweig, Germany [2] Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.Journal
Molecular systems biologyPubMed ID
23169000Type
ArticleLanguage
enISSN
1744-4292ae974a485f413a2113503eed53cd6c53
10.1038/msb.2012.56
Scopus Count
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