dc.contributor.author | Sadreev, II | |
dc.contributor.author | Chen, MZQ | |
dc.contributor.author | Umezawa, Y | |
dc.contributor.author | Biktashev, VN | |
dc.contributor.author | Kemper, C | |
dc.contributor.author | Salakhieva, DV | |
dc.contributor.author | Welsh, GI | |
dc.contributor.author | Kotov, NV | |
dc.date.accessioned | 2017-02-14T09:49:38Z | |
dc.date.issued | 2017-10-14 | |
dc.description.abstract | Signal transducers and activators of transcription (STATs) are key molecular determinants of T cell fate and effector function. A number of inflammatory diseases are characterized by an altered balance of T cell phenotypes and cytokine secretion. STATs, therefore, represent viable therapeutic targets in numerous pathologies. However, the underlying mechanisms of how the same STAT proteins regulate both the development of different T cell phenotypes and their plasticity during changes in extracellular conditions remain unclear. In this study, we investigated the STAT mediated regulation of T cell phenotype formation and plasticity using mathematical modeling and experimental data for intracellular STAT signaling proteins. The close fit of our model predictions to the experimental data for IFN-{\gamma} to IL-10 switching allows us to propose a potential mechanism for T cell switching that regulates human Th1/Tr1 responses. According to this mechanism, T cell phenotype switching is due to the relative redistribution of STAT dimer complexes caused by the extracellular cytokine-dependent STAT competition effects. The proposed model is applicable to a number of STAT signaling circuits. | en_GB |
dc.identifier.citation | Vol. 153 (4), pp. 488-501 | en_GB |
dc.identifier.doi | 10.1111/imm.12851 | |
dc.identifier.uri | http://hdl.handle.net/10871/25826 | |
dc.language.iso | en | en_GB |
dc.publisher | Wiley | en_GB |
dc.title | The competitive nature of signal transducer and activator of transcription complex formation drives phenotype switching of T cells | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2017-02-14T09:49:38Z | |
dc.description | This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record | en_GB |
dc.identifier.journal | Immunology | en_GB |