biostudies-otherUnknown12Denis ThieffryScience signalingeaar3641https://www.ebi.ac.uk/biostudies/studies/MODEL1903260003biostudies-other30992399Denis ThieffryKausthubh RamachandranfalseRodríguez-Jorge2019 - Boolean model of combined TCR and TLR5 signaling for CD4 + T cell activationCD4+ 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.2019-03-26T00:00:00Z2025-07-14T17:49:45.521Z2025-03-30T22:45:38.127ZMODEL190326000330992399MAMO_0000030null