PPAR gamma Negatively Regulates T Cell Activation to Prevent Follicular Helper T Cells and Germinal Center Formation
- Authors
- Park, Hong-Jai; Kim, Do-Hyun; Choi, Jin-Young; Kim, Won-Ju; Kim, Ji Yun; Senejani, Alireza G.; Hwang, Soo Seok; Kim, Lark Kyun; Tobiasova, Zuzana; Lee, Gap Ryol; Craft, Joseph; Bothwell, Alfred L. M.; Choi, Je-Min
- Issue Date
- Jun-2014
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.9, no.6, pp.1 - 11
- Indexed
- SCIE
SCOPUS
- Journal Title
- PLOS ONE
- Volume
- 9
- Number
- 6
- Start Page
- 1
- End Page
- 11
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/144654
- DOI
- 10.1371/journal.pone.0099127
- ISSN
- 1932-6203
- Abstract
- Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a transcription factor that regulates lipid and glucose metabolism. Although studies of PPAR gamma 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-PPAR gamma(KO) mice to investigate PPAR gamma-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 I kappa B alpha, Sirt1, and Foxo1, which are inhibitors of NF-kappa B, was observed in PPAR gamma-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-PPAR gamma(KO) 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 T-FH cells and germinal centers in CD4-PPAR gamma(KO) 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 PPAR gamma has a regulatory role for T-FH cells and germinal center reaction to prevent autoimmunity.
- Files in This Item
-
Go to Link
- Appears in
Collections - 서울 자연과학대학 > 서울 생명과학과 > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.