The nuclear receptor PPARγ regulates T cell tolerance and germinal center formation via generation of follicular helper T cells (P4545)

Abstract Peroxisome proliferator-activated receptor gamma (PPARγ) acts as a transcription factor to regulate lipid and glucose metabolism. An emerging role of PPARγ has been suggested that it has important regulatory functions in inflammation and adaptive immunity. However, the intrinsic role of PPARγ in T cells is not fully understood. Here we used CD4-PPARγKO mice to understand the function of PPARγ in T cells. PPARγ deficient T cells produced higher levels of cytokines including IFN-γ, IL-17, or IL-2, and proliferated more than wild type T cells following TcR stimulation with increased phosphorylation of ERK and AKT. Interestingly, PPARγ deficient T cells were prone to differentiate into various helper T cell subsets such as Th1, Th2, Th17, and Th9 cells. Furthermore, aged mice with PPARγ deficient T cells showed increased numbers of follicular helper T cells (TFH cells) and spontaneously develop a moderate autoimmune phenotype with kidney inflammation, enhanced autoantibody production and increased numbers of germinal centers. The abrogation of T cell tolerance was further confirmed with the diminished the expression of IkBα, Sirt1, and Foxo1 to inhibit NF-κB. These results suggest that PPARγ is crucial for maintaining T cell tolerance and germinal center formation and TFH generation to prevent autoimmunity.