Dendritic Cells and the Establishment of Fetomaternal Tolerance for Successful Human Pregnancy

Pregnancy is a remarkable event where the semi-allogeneic fetus develops in the mother’s uterus, despite genetic and immunological differences. The antigen handling and processing at the maternal–fetal interface during pregnancy appear to be crucial for the adaptation of the maternal immune system and for tolerance to the developing fetus and placenta. Maternal antigen-presenting cells (APCs), such as macrophages (Mφs) and dendritic cells (DCs), are present at the maternal–fetal interface throughout pregnancy and are believed to play a crucial role in this process. Despite numerous studies focusing on the significance of Mφs, there is limited knowledge regarding the contribution of DCs in fetomaternal tolerance during pregnancy, making it a relatively new and growing field of research. This review focuses on how the behavior of DCs at the maternal–fetal interface adapts to pregnancy’s unique demands. Moreover, it discusses how DCs interact with other cells in the decidual leukocyte network to regulate uterine and placental homeostasis and the local maternal immune responses to the fetus. The review particularly examines the different cell lineages of DCs with specific surface markers, which have not been critically reviewed in previous publications. Additionally, it emphasizes the impact that even minor disruptions in DC functions can have on pregnancy-related complications and proposes further research into the potential therapeutic benefits of targeting DCs to manage these complications.