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

ABSTRACT

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.

KEYWORDS:

• IDO
• interferon-γ
• maternal-fetal tolerance
• reproductive hormones

Funding

Grant # 2009/54597-2, São Paulo Research Foundation (FAPESP).

Additional information

Funding

Grant # 2009/54597-2, São Paulo Research Foundation (FAPESP).