14:10-14:30 Dendritic cells and Tregs interplay at the maternal-fetal interface

Successful pregnancies depend on maternal-fetal tolerance. Understanding the immune mechanisms of infertility and recurrent miscarriage is mandatory to improve care. We previously established that maternal CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) are necessary to protect the fetus from maternal immune response (1). We also discovered that self-specific thymic-derived Tregs accumulate in the uterus-draining lymph nodes (LNs) and uterus and protect embryos at implantation (2, 3). These cells are dependent on antigen-presenting cells and especially on dendritic cells (DCs), the immune sentinels that capture, process and present self and foreign antigens to T cells in order to initiate immune response or promote immune tolerance depending on the context. Unfortunately, little is known about the DCs of the maternofetal interface and their role in normal or pathological pregnancy. We examined the dynamics of Dendritic Cells (DCs) subsets from pregnant and non-pregnant mice and humans during normal or pathological pregnancies, and we investigated the consequences of DCs deficiency on pregnancy in genetically-modified mice and in humans. We show how DCs influence the homeostasis of Treg cells as well as the homeostasis of Natural Killer (NK) cells during pregnancy. We also show and discuss how the modulation of the homeostasis of specific DC subsets affects the outcome of pregnancy and can be used to cure implantation failure and multiple miscarriages. Our results may help to improve prenatal diagnosis and serve as a foundation for designing innovative biotherapies for patients with infertility problems and multiple miscarriages.