Systems Modeling of Molecular Mechanisms Controlling Cytokine-driven CD4+ T Cell Differentiation and Phenotype Plasticity
Figure 2
Activation of peroxisome proliferator-activated receptor γ (PPARγ) regulates differentiation of CD4+ T cells.
(A) Computational simulation of the effect of in silico activation of PPARγ in a T helper (Th)17 cell on the levels of FOXP3, IL-17 and RORγt. (B) PPARγ inhibits Th17 differentiation. Naïve wild-type CD4+ T cells differentiated with IL-6 in combination with TGF-β in vitro for 60h express less RORγt and produce lower levels of IL-17A when compared to T cell-specific PPARγ null Th17 cells. (C) Increasing concentrations of pioglitazone (PIO), a full PPARγ agonist, upregulate FOXP3 in wild-type Th17 differentiated cells following 24 h treatment and down-regulate RORγt and IL-17A in wild-type cells. (D) Increasing concentrations of PIO do not have an effect in PPARγ null Th17 cells. The double-positive region can be observed in the upper right part of the flow plots.