CD4+ T cell differentiation studies

Th17 cells mediate inflammatory and effector responses during infectious and immune-mediated diseases. The mechanisms of action modulating the plasticity between Th17 and Treg cells are incompletely understood. To gain a better understanding of the differentiation process we have constructed a computational model in COPASI that mimics CD4+ T cell differentiation and contemplates the plasticity between effector Th17 and Treg. Our computer simulations predicted that activation of peroxisome proliferator activated receptor gamma (PPARg) induces a switch from already differentiated Th17 into Treg. Experimental validation approaches support this in silico prediction. The conclusion of this project is that PPARg promotes differentiation of naive CD4+ T cells into Treg, downregulates Th17 differentiation and favors phenotype switch from Th17 into Treg cells.