Progesterone Decreases in vitro Indoleamine 2, 3-dioxygenase Expression in Dendritic and CD4+ Cells from Maternal-Fetal Interface of Rats

• Published in: Immunological investigations Vol. 46; no. 5; pp. 447 - 459
• Main Authors: Bianchi, Pedro Kastein Faria da Cunha, Leandro, Rafael Magdanelo, Poscai, Aline Nayara, Yoshinaga, Tulio, Gonçalez, Patrícia Orlandini, Kfoury Junior, José Roberto
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04.07.2017
• Subjects: Abortifacient Agents, Steroidal - pharmacology; Animals; Apoptosis - drug effects; Apoptosis - genetics; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Embryo, Mammalian; Female; Gene Expression Regulation; IDO; Immune Tolerance - drug effects; Immunophenotyping; Indoleamine-Pyrrole 2,3,-Dioxygenase - antagonists & inhibitors; Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics; Indoleamine-Pyrrole 2,3,-Dioxygenase - immunology; Interferon-gamma - pharmacology; interferon-γ; Maternal-Fetal Exchange - immunology; maternal-fetal tolerance; Mifepristone - pharmacology; Placenta - cytology; Placenta - drug effects; Placenta - immunology; Pregnancy; Primary Cell Culture; Progesterone - pharmacology; Rats; Rats, Wistar; Receptors, Progesterone - antagonists & inhibitors; Receptors, Progesterone - genetics; Receptors, Progesterone - immunology; reproductive hormones; Tryptophan - immunology; Tryptophan - metabolism; Uterus - cytology; Uterus - drug effects; Uterus - immunology; interferon-γ; reproductive hormones; IDO; maternal-fetal tolerance
• ISSN: 0882-0139; 1532-4311
• DOI: 10.1080/08820139.2017.1296856

Problem: Several mechanisms contribute to the tolerogenic state observed during pregnancy, such as the activity of the enzyme indoleamine 2, 3-dioxygenase (IDO). This initializes the catabolism of tryptophan, inducing T cells to apoptosis due to its deprivation and by the action of its catabolites in the placental microenvironment. Progesterone plays an important part on immunological tolerance mechanisms during pregnancy; however, there is no evidence it is related to IDO activity. Thus, this study aimed to investigate progesterone influence on the maternal-fetal interface of pregnant Wistar rats, by identifying IDO positive cells by immunophenotyping and flow cytometry under exogenous progesterone supplementation. Method of study: Placenta and embryo cells were cultured and separated into groups that received interferon γ or progesterone, supplemented or not with mifepristone. After 2 and 24 h, these were labeled with an anti-IDO and a series of antibodies specific to leucocytes and progesterone receptor and processed through flow cytometry analysis. Results: Progesterone induced a significant decrease in the expression of IDO in dendritic cells and CD4 + lymphocytes. Conclusion: The blocking of progesterone receptor on these cells by mifepristone restored IDO expression levels and may constitute evidence of the participation of this hormone through a direct route in these cells.