Open AccessPLAU inferred from a correlation network is critical for suppressor function of regulatory T cells
Author(s) -
He Feng,
Chen Hairong,
ProbstKepper Michael,
Geffers Robert,
Eifes Serge,
del Sol Antonio,
Schughart Klaus,
Zeng AnPing,
Balling Rudi
Publication year - 2012
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2012.56
Subject(s) - biology , function (biology) , suppressor , correlation , gene regulatory network , computational biology , genetics , microbiology and biotechnology , gene , gene expression , mathematics , geometry
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.