Dataset Information

Rodríguez-Jorge2019 - Boolean model of combined TCR and TLR5 signaling for CD4 + T cell activation

ABSTRACT: 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.

SUBMITTER: Denis Thieffry

PROVIDER: MODEL1903260003 | BioModels | 2021-04-06

REPOSITORIES: BioModels

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			Action	DRS
	MODEL1903260003?filename=RodriguezJorge_Merged_TCR_TLR5_Signalling_BooleanModel_15Jul2018.sbml	Other

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Publications

Cooperation between T cell receptor and Toll-like receptor 5 signaling for CD4<sup>+</sup> T cell activation.

Rodríguez-Jorge Otoniel O Kempis-Calanis Linda A LA Abou-Jaoudé Wassim W Gutiérrez-Reyna Darely Y DY Hernandez Céline C Ramirez-Pliego Oscar O Thomas-Chollier Morgane M Spicuglia Salvatore S Santana Maria A MA Thieffry Denis D

Science signaling 20190416 577

CD4<sup>+</sup> 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 TC ...[more]

PMID: 30992399

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