| First Author | Park HJ | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 6 | Pages | e99127 |
| PubMed ID | 24921943 | Mgi Jnum | J:218565 |
| Mgi Id | MGI:5617919 | Doi | 10.1371/journal.pone.0099127 |
| Citation | Park HJ, et al. (2014) PPARgamma negatively regulates T cell activation to prevent follicular helper T cells and germinal center formation. PLoS One 9(6):e99127 |
| abstractText | Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription factor that regulates lipid and glucose metabolism. Although studies of PPARgamma ligands have demonstrated its regulatory functions in inflammation and adaptive immunity, its intrinsic role in T cells and autoimmunity has yet to be fully elucidated. Here we used CD4-PPARgammaKO mice to investigate PPARgamma-deficient T cells, which were hyper-reactive to produce higher levels of cytokines and exhibited greater proliferation than wild type T cells with increased ERK and AKT phosphorylation. Diminished expression of IkappaBalpha, Sirt1, and Foxo1, which are inhibitors of NF-kappaB, was observed in PPARgamma-deficient T cells that were prone to produce all the signature cytokines under Th1, Th2, Th17, and Th9 skewing condition. Interestingly, 1-year-old CD4-PPARgammaKO mice spontaneously developed moderate autoimmune phenotype by increased activated T cells, follicular helper T cells (TFH cells) and germinal center B cells with glomerular inflammation and enhanced autoantibody production. Sheep red blood cell immunization more induced TFH cells and germinal centers in CD4-PPARgammaKO mice and the T cells showed increased of Bcl-6 and IL-21 expression suggesting its regulatory role in germinal center reaction. Collectively, these results suggest that PPARgamma has a regulatory role for TFH cells and germinal center reaction to prevent autoimmunity. |
