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PLoS One. 2014 Jun 12;9(6):e99127. doi: 10.1371/journal.pone.0099127. eCollection 2014.

PPARγ negatively regulates T cell activation to prevent follicular helper T cells and germinal center formation.

Author information

1
Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea; Hanyang Biomedical Research Institute, Seoul, Korea.
2
Department of Internal Medicine (Rheumatology), Yale University School of Medicine, New Haven, Connecticut, United States of America.
3
Department of Therapeutic Radiology and Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
4
Department of Life Science, Sogang University, Seoul, Korea.
5
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
6
Department of Internal Medicine (Rheumatology), Yale University School of Medicine, New Haven, Connecticut, United States of America; Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates lipid and glucose metabolism. Although studies of PPARγ 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-PPARγKO mice to investigate PPARγ-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 IκBα, Sirt1, and Foxo1, which are inhibitors of NF-κB, was observed in PPARγ-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-PPARγKO 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-PPARγKO 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 PPARγ has a regulatory role for TFH cells and germinal center reaction to prevent autoimmunity.

PMID:
24921943
PMCID:
PMC4055678
DOI:
10.1371/journal.pone.0099127
[Indexed for MEDLINE]
Free PMC Article

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