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

Hong Jai Park, Do Hyun Kim, Jin Young Choi, Won Ju Kim, Ji Yun Kim, Alireza G. Senejani, Soo Seok Hwang, Lark Kyun Kim, Zuzana Tobiasova, Gap Ryol Lee, Joseph Craft, Alfred L.M. Bothwell, Je Min Choi

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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 (T FH 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.

Original languageEnglish (US)
Article numbere99127
JournalPloS one
Volume9
Issue number6
DOIs
StatePublished - Jun 12 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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