title: Effect of progesterone on Th1/Th2/Th17 and regulatory T cell-related genes in peripheral blood mononuclear cells during pregnancy in cows.
abstract: 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.
authors.affiliation: Laboratory of Large Animal Internal Medicine, Faculty of Veterinary Medicine, Kitasato University, 35-1 Higashi 23 bancho, Towada, Aomori, 034-8628, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Maeda
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ohtsuka
authors.forename: Michiko
authors.initials: M
authors.lastname: Tomioka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oikawa
mesh_terms: D000818:Animals; D002417:Cattle; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011247:Pregnancy; D011374:Progesterone / Q000097:blood*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D011980:Receptors, Progesterone; D014157:Transcription Factors; D011374:Progesterone