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dc.contributor.authorHe, Feng
dc.contributor.authorChen, Hairong
dc.contributor.authorProbst-Kepper, Michael
dc.contributor.authorGeffers, Robert
dc.contributor.authorEifes, Serge
dc.contributor.authorDel Sol, Antonio
dc.contributor.authorSchughart, Klaus
dc.contributor.authorZeng, An-Ping
dc.contributor.authorBalling, Rudi
dc.date.accessioned2012-12-12T10:43:05Zen
dc.date.available2012-12-12T10:43:05Zen
dc.date.issued2012-11-20en
dc.identifier.citationPLAU inferred from a correlation network is critical for suppressor function of regulatory T cells. 2012, 8:624 Mol. Syst. Biol.en_GB
dc.identifier.issn1744-4292en
dc.identifier.pmid23169000en
dc.identifier.doi10.1038/msb.2012.56en
dc.identifier.urihttp://hdl.handle.net/10033/255463en
dc.description.abstractHuman 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.
dc.language.isoenen
dc.rightsArchived with thanks to Molecular systems biologyen_GB
dc.titlePLAU inferred from a correlation network is critical for suppressor function of regulatory T cells.en
dc.typeArticleen
dc.contributor.department1] 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.en_GB
dc.identifier.journalMolecular systems biologyen_GB
refterms.dateFOA2018-06-13T09:23:54Z
html.description.abstractHuman 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.


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