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

• Published in: Veterinary research communications 2013-03, Vol.37 (1), p.43-49
• Main Authors: Maeda, Yousuke, Ohtsuka, Hiromichi, Tomioka, Michiko, Oikawa, Masaaki
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Cattle; Cytokines - genetics; Cytokines - metabolism; Female; Gene Expression Regulation; Leukocytes, Mononuclear - metabolism; Life Sciences; Original Article; Polymerase Chain Reaction - veterinary; Pregnancy; Progesterone - blood; Receptors, Progesterone - genetics; Receptors, Progesterone - metabolism; T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Regulatory - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Veterinary Medicine/Veterinary Science; Zoology
• ISSN: 0165-7380; 1573-7446
• DOI: 10.1007/s11259-012-9545-7

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 μg/ml, and the mRNA expression of Th1, Th2, Th17 and Treg-related cytokines (IFN-γ, IL-4, IL-17 and TGF-β), 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-γ and IL-17 dose-dependently, whereas P 4 did not affect the expression of TGF-β 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.