Event Abstract Back to Event Identification of PLAU as a critical gene for the suppressive function of memory-like CD4+ regulatory T cells Feng Q. He1*, Hairong Chen2, Michael Probst-Kepper3, Robert Geffers4, Serge Eifes1, Antonio Del Sol1, Klaus Schughart2, An-Ping Zeng5 and Rudi Balling1 1 Luxembourg Centre for Systems Biology, University of Luxembourg, Luxembourg 2 Helmholtz Centre for Infection Research, Department of Infection Genetics, Germany 3 Institute of Microbiology, Immunology and Hospital Hygiene, Städtisches Klinikum Braunschweig GmbH, Germany 4 Helmholtz Centre for Infection Research, Department of Cell Biology, Germany 5 Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology, Germany The plasminogen activator urokinase (PLAU) is known for its role in fibrinolysis and late-onset Alzheimer diseases. However, we here demonstrate that PLAU is also important for the suppressor function of both human and murine CD4+ regulatory T cells (Tregs). The prediction of PLAU as an important gene is made through a systems biological network strategy directly from an undirected Treg-specific correlation network which we reconstruct from a high-time-resolution transcriptome during the very early activation process of human Tregs/CD4+ T-effector cells (Teffs). First of all, our results show that both mRNA and membrane-bound cell-surface protein expression of PLAU are significantly higher in activated Tregs than activated Teffs in a time-course measurement. The validation results show that the membrane-bound PLAU regulates the expression of several known Treg key genes, e.g., FOXP3 and EOS and others. Moreover, our analysis unveils that PLAU is particularly important for memory-like CD44highCD62Llow but not CD44lowCD62Lhigh Tregs. Detailed mechanistic investigation shows that PLAU mediates Treg suppressor function via STAT5 and ERK signaling pathways but not via PLAU-PLAUR interaction between Treg and Teffs. Further analysis also shows that the development of the thymic Cd4+Cd25+Foxp3+ Tregs was significantly enhanced in Plau-/-mice, which might compensate the impaired suppressive function of memory-like Tregs and consequently not generate spontaneous autoimmune disorders. Our study highlights not only the power of the proposed network strategy but also a critical role for PLAU in Treg suppressor function. References Feng He, Hairong Chen, Michael Probst-Kepper, Robert Geffers, Serge Eifes, Antonio del Sol, Klaus Schughart, An-Ping Zeng and Rudi Balling (2012), PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells, Molecular Systems Biology, 8, 624 Keywords: plasminogen activator urokinase (PLAU or UPA), regulatory T cells, suppressor function, development, Systems Biology, correlation network Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: He FQ, Chen H, Probst-Kepper M, Geffers R, Eifes S, Del Sol A, Schughart K, Zeng A and Balling R (2013). Identification of PLAU as a critical gene for the suppressive function of memory-like CD4+ regulatory T cells. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00828 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Feng Q He, Luxembourg Centre for Systems Biology, University of Luxembourg, Esch-Belval, L-4362, Luxembourg, fenghe01@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Feng Q He Hairong Chen Michael Probst-Kepper Robert Geffers Serge Eifes Antonio Del Sol Klaus Schughart An-Ping Zeng Rudi Balling Google Feng Q He Hairong Chen Michael Probst-Kepper Robert Geffers Serge Eifes Antonio Del Sol Klaus Schughart An-Ping Zeng Rudi Balling Google Scholar Feng Q He Hairong Chen Michael Probst-Kepper Robert Geffers Serge Eifes Antonio Del Sol Klaus Schughart An-Ping Zeng Rudi Balling PubMed Feng Q He Hairong Chen Michael Probst-Kepper Robert Geffers Serge Eifes Antonio Del Sol Klaus Schughart An-Ping Zeng Rudi Balling Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.