TY - JOUR
T1 - Sex-based selectivity of PPARγ regulation in Th1, Th2, and Th17 differentiation
AU - Park, Hong Jai
AU - Park, Hyeon Soo
AU - Lee, Jae Ung
AU - Bothwell, Alfred L.M.
AU - Choi, Je Min
N1 - Funding Information:
This work was supported by grants from the Basic Science Research Program through the National Research Foundation of Korea (NRF-2013R1A1A2A10060048) and by the research fund of Hanyang University (HY-2013-00000001472) to Je-Min Choi.
Publisher Copyright:
© 2016 by the authors; licensee MDPI, Basel, Switzerland.
PY - 2016/8/18
Y1 - 2016/8/18
N2 - 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.
AB - 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.
KW - Effector T cells
KW - Estrogen
KW - PPARγ
KW - Pioglitazone
KW - Sex
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U2 - 10.3390/ijms17081347
DO - 10.3390/ijms17081347
M3 - Article
C2 - 27548145
AN - SCOPUS:84983491154
SN - 1661-6596
VL - 17
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 8
M1 - 1347
ER -