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Int. J. Mol. Sci. 2016, 17(8), 1347;

Sex-Based Selectivity of PPARγ Regulation in Th1, Th2, and Th17 Differentiation

Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Korea
Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon 16419, Korea
Author to whom correspondence should be addressed.
Academic Editor: Béatrice Desvergne
Received: 13 June 2016 / Revised: 3 August 2016 / Accepted: 11 August 2016 / Published: 18 August 2016
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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. View Full-Text
Keywords: PPARγ; pioglitazone; effector T cells; estrogen; sex PPARγ; pioglitazone; effector T cells; estrogen; sex

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Park, H.-J.; Park, H.-S.; Lee, J.-U.; Bothwell, A.L.M.; Choi, J.-M. Sex-Based Selectivity of PPARγ Regulation in Th1, Th2, and Th17 Differentiation. Int. J. Mol. Sci. 2016, 17, 1347.

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