10.3389/fphys.2018.00877.s007
Mariana E. Martinez-Sanchez
Mariana E.
Martinez-Sanchez
Leonor Huerta
Leonor
Huerta
Elena R. Alvarez-Buylla
Elena
R. Alvarez-Buylla
Carlos Villarreal Luján
Carlos Villarreal
Luján
Data_Sheet_7_Role of Cytokine Combinations on CD4+ T Cell Differentiation, Partial Polarization, and Plasticity: Continuous Network Modeling Approach.ZIP
Frontiers
2018
CD4+ T cells
regulatory network
ODE
heterogeneity
plasticity
micro-environment
cytokines
2018-08-06 16:08:40
Dataset
https://frontiersin.figshare.com/articles/dataset/Data_Sheet_7_Role_of_Cytokine_Combinations_on_CD4_T_Cell_Differentiation_Partial_Polarization_and_Plasticity_Continuous_Network_Modeling_Approach_ZIP/6936365
<p>Purpose: We put forward a theoretical and dynamical approach for the semi-quantitative analysis of CD4+ T cell differentiation, the process by which cells with different functions are derived from activated CD4<sup>+</sup> T naïve lymphocytes in the presence of particular cytokine microenvironments. We explore the system-level mechanisms that underlie CD4+ T plasticity-the conversion of polarized cells to phenotypes different from those originally induced.</p><p>Methods: In this paper, we extend a previous study based on a Boolean network to a continuous framework. The network includes transcription factors, signaling pathways, as well as autocrine and exogenous cytokines, with interaction rules derived using fuzzy logic.</p><p>Results: This approach allows us to assess the effect of relative differences in the concentrations and combinations of exogenous and endogenous cytokines, as well as of the expression levels of diverse transcription factors. We found either abrupt or gradual differentiation patterns between observed phenotypes depending on critical concentrations of single or multiple environmental cytokines. Plastic changes induced by environmental cytokines were observed in conditions of partial phenotype polarization in the T helper 1 to T helper 2 transition. On the other hand, the T helper 17 to induced regulatory T-cells transition was highly dependent on cytokine concentrations, with TGFβ playing a prime role.</p><p>Conclusion: The present approach is useful to further understand the system-level mechanisms underlying observed patterns of CD4<sup>+</sup> T differentiation and response to changing immunological challenges.</p>