Figure 2
Proposed roles of uDCs in the regulation of angiogenesis and T cell action at the maternal-fetal interface.
During pregnancy, monocytes are recruited to the uterus, where they differentiate into mature tolerogenic cells such as uDCs, under the influence of CSF-1, GM-CSF, and other cytokines (usually IL-4, although this cytokine has not been found in the uterus). uDCs produce sFLT1 and TGF-β1, which act to maintain the intricate balance of vascular development: sFLT1 modulates the actions of VEGF, and TGF-β1 influences endothelial cell viability and vascular maturation. This fine-tuning of angiogenesis is required for decidualization and embryo implantation. In addition, other studies have shown that TGF-β1 is presented by DCs at their surface on αvβ8 integrin. TGF-β1 suppresses cytotoxic CD8+ T cell function and promotes the development of Tregs. These data suggest that in addition to their role in decidual development, as shown in the present study by Plaks et al (7), uDCs also play a role in immunoregulation. Together, these dual functions of uDCs contribute to successful implantation and the progression of an allogeneic pregnancy. This whole process is further coordinated during implantation and decidualization by the uterine synthesis of the growth factors VEGF and CSF-1 under the control of the ovarian hormones E2 and P4 (see Figure 1), which are the master regulators of pregnancy.
