Cooperation between T cell receptor and Toll-like receptor 5 signaling for CD4 + T cell activation

• Published in: Science signaling Vol. 12; no. 577
• Main Authors: Rodríguez-Jorge, Otoniel, Kempis-Calanis, Linda A, Abou-Jaoudé, Wassim, Gutiérrez-Reyna, Darely Y, Hernandez, Céline, Ramirez-Pliego, Oscar, Thomas-Chollier, Morgane, Spicuglia, Salvatore, Santana, Maria A, Thieffry, Denis
• Format: Journal Article
• Language: English
• Published: United States 16.04.2019
• ISSN: 1937-9145
• DOI: 10.1126/scisignal.aar3641

CD4 T cells recognize antigens through their T cell receptors (TCRs); however, additional signals involving costimulatory receptors, for example, CD28, are required for proper T cell activation. Alternative costimulatory receptors have been proposed, including members of the Toll-like receptor (TLR) family, such as TLR5 and TLR2. To understand the molecular mechanism underlying a potential costimulatory role for TLR5, we generated detailed molecular maps and logical models for the TCR and TLR5 signaling pathways and a merged model for cross-interactions between the two pathways. Furthermore, we validated the resulting model by analyzing how T cells responded to the activation of these pathways alone or in combination, in terms of the activation of the transcriptional regulators CREB, AP-1 (c-Jun), and NF-κB (p65). Our merged model accurately predicted the experimental results, showing that the activation of TLR5 can play a similar role to that of CD28 activation with respect to AP-1, CREB, and NF-κB activation, thereby providing insights regarding the cross-regulation of these pathways in CD4 T cells.