Sex-based selectivity of PPARγ regulation in Th1, Th2, and Th17 differentiation

Hong Jai Park, Hyeon Soo Park, Jae Ung Lee, Alfred L.M. Bothwell, Je Min Choi

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) has recently been recognized to regulate adaptive immunity through Th17 differentiation, Treg functions, and TFH responses. However, its role in adaptive immunity and autoimmune disease is still not clear, possibly due to sexual differences. Here, we investigated in vitro treatment study with the PPARγ agonist pioglitazone to compare Th1, Th2, and Th17 differentiation in male and female mouse splenic T cells. Pioglitazone treatment significantly inhibited various effector T cell differentiations including Th1, Th2, and Th17 cells from female naïve T cells, but it selectively reduced IL-17 production in male Th17 differentiation. Interestingly, pioglitazone and estradiol (E2) co-treatment of T cells in males inhibited differentiation of Th1, Th2, and Th17 cells, suggesting a mechanism for the greater sensitivity of PPARγ to ligand treatment in the regulation of effector T cell differentiation in females. Collectively, these results demonstrate that PPAR selectively inhibits Th17 differentiation only in male T cells and modulates Th1, Th2, and Th17 differentiation in female T cells based on different level of estrogen exposure. Accordingly, PPARγ could be an important immune regulator of sexual differences in adaptive immunity.

Original languageEnglish (US)
Article number1347
JournalInternational journal of molecular sciences
Volume17
Issue number8
DOIs
StatePublished - Aug 18 2016
Externally publishedYes

Keywords

  • Effector T cells
  • Estrogen
  • PPARγ
  • Pioglitazone
  • Sex

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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