title: Sex-Based Selectivity of PPARγ Regulation in Th1, Th2, and Th17 Differentiation.
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 PPARγ 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.
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Korea. hongjai@hanyang.ac.kr.|Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea. hongjai@hanyang.ac.kr.
authors.forename: Hong-Jai
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Korea. hspark91@hanyang.ac.kr.|Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea. hspark91@hanyang.ac.kr.
authors.forename: Hyeon-Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Korea. jaeunglee@hanyang.ac.kr.|Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea. jaeunglee@hanyang.ac.kr.
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. alfred.bothwell@yale.edu.
authors.forename: Alfred L M
authors.initials: AL
authors.lastname: Bothwell
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Korea. jeminchoi@hanyang.ac.kr.|Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea. jeminchoi@hanyang.ac.kr.|Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 16419, Korea. jeminchoi@hanyang.ac.kr.
authors.forename: Je-Min
authors.initials: JM
authors.lastname: Choi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D000077205:Pioglitazone; D012737:Sex Factors; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D004967:Estrogens; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: PPARγ; effector T cells; estrogen; pioglitazone; sex