title: Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogen.
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.
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 133-791, Republic of Korea.|Research Institute for Natural Sciences, Seoul, 133-791, Republic of Korea.
authors.forename: Hong-Jai
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 133-791, Republic of Korea.|Research Institute for Natural Sciences, Seoul, 133-791, Republic of Korea.
authors.forename: Hyeon-Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 133-791, Republic of Korea.|Research Institute for Natural Sciences, Seoul, 133-791, Republic of Korea.
authors.forename: Jae-Ung
authors.initials: JU
authors.lastname: Lee
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Alfred L M
authors.initials: AL
authors.lastname: Bothwell
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 133-791, Republic of Korea.|Research Institute for Natural Sciences, Seoul, 133-791, Republic of Korea.|Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 440-746, Republic of Korea.
authors.forename: Je-Min
authors.initials: JM
authors.lastname: Choi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015704:CD4 Antigens / Q000172:deficiency / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D018858:Germinal Center / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry; D010047:Ovalbumin / Q000276:immunology; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000077205:Pioglitazone; D012737:Sex Factors; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D015704:CD4 Antigens; D047495:PPAR gamma; D045162:Thiazolidinediones; D004958:Estradiol; D010047:Ovalbumin; D000077205:Pioglitazone