Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogen

Sci Rep. 2016 Jun 23:6:28495. doi: 10.1038/srep28495.

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ), a master regulator of adipocyte differentiation, has recently been connected with effector T cells, though its role is still not clear. Here, we investigated the roles of PPARγ in follicular helper T (TFH) cell responses regarding gender specificity. NP-OVA immunization in female but not male CD4-PPARγ(KO) mice induced higher proportions of TFH cells and germinal center (GC) B cells following immunization than were seen in wild type mice. Treatment with the PPARγ agonist pioglitazone significantly reduced TFH cell responses in female mice while pioglitazone and estradiol (E2) co-treatment ameliorated TFH cells and GC responses in male mice. E2 treatment significantly enhanced PPARγ expression in male T cells, while T cell activation in the estrus but not in the diestrus stage of the menstrual cycle of females was inhibited by pioglitazone, suggesting that an estrogen-sufficient environment is important for PPARγ-mediated T cell regulation. These results demonstrate gender-based differences in sensitivities of PPARγ in TFH responses. These findings suggest that appropriate function of PPARγ is required in the regulation of female GC responses and that therapeutic strategies for autoimmune diseases using PPARγ agonists need to be tailored accordingly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • CD4 Antigens / deficiency
  • CD4 Antigens / genetics
  • Estradiol / pharmacology*
  • Female
  • Flow Cytometry
  • Germinal Center / drug effects
  • Germinal Center / immunology
  • Germinal Center / metabolism
  • Lymphocyte Activation / drug effects*
  • Male
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Nanoparticles / chemistry
  • Ovalbumin / immunology
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Pioglitazone
  • Sex Factors
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Thiazolidinediones / pharmacology

Substances

  • CD4 Antigens
  • PPAR gamma
  • Thiazolidinediones
  • Estradiol
  • Ovalbumin
  • Pioglitazone