PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells

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.

Subjects

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

DDC Class

570: Biowissenschaften, Biologie

Lizenz

https://creativecommons.org/licenses/by-nc-sa/3.0/

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624.full-1.pdf

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941.08 KB

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PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells