Effect of progesterone on Th1/Th2/Th17 and Regulatory T cell-related genes in peripheral blood mononuclear cells during pregnancy in cows

T helper (Th) cells play a central role in immune responses and new Th1/Th2/Th17 and regulatory T (Treg)-cell paradigm in pregnancy has developed. Progesterone (P-4) is essential for the maintenance of pregnancy; however the effect of P-4 on Th1/Th2/Th17 and Treg paradigm is unclear in cows. We evaluated the effect of P-4 on the expression of Th1/Th2/Th17 and Treg-related cytokines, transcription factors, and P-4 receptors in the peripheral blood mononuclear cells (PBMCs) from 8 pregnant (163.1 +/- 16.9 days of gestation) and 8 non-pregnant luteal phase cows. PBMCs were stimulated with P-4 at 0, 0.1, 1 or 10 mu g/ml, and the mRNA expression of Th1, Th2, Th17 and Treg-related cytokines (IFN-gamma, IL-4, IL-17 and TGF-beta), transcription factors (T-bet, GATA-3, RORC and Foxp3) and P-4 receptors (PGR, PGRMC1 and PGRMC2) were analyzed by real time RT-PCR. In both pregnant and non-pregnant cows, P-4 significantly inhibited the expression of IFN-gamma and IL-17 dose-dependently, whereas P-4 did not affect the expression of TGF-beta and Foxp3. In addition, P-4 significantly decreased the expression of T-bet and RORC, and enhanced the expression of IL-4 in the pregnant cows, but this reaction was not found in the non-pregnant cows. P-4 tended to increase PGRMC1 in the pregnant cows but not in the non-pregnant cows, indicating that PGRMC1 may be involved in the regulation of the effect of P-4 during bovine pregnancy. These results indicate that P-4 is an important regulator of Th1/Th2/Th17 and Treg immunity, and higher Th2 immunity is characteristic in the pregnant cows.