Dendritic Cells in Implantation: New Players During the Angiogenesis Process.

Abstract

Implantation of mammalian embryos into their mother's uterus ensures optimal nourishment and protection throughout development. Successful pregnancy relies on the establishment of an adequate blood supply to support the metabolic demands of the growing embryo/fetus. Pregnancy is indeed one of the unique situations in which angiogenesis (the development of new blood vessels from pre-existing ones) takes place under physiological conditions. A delicate balance between stimulatory and inhibitory signals regulates angiogenic responses in the decidua, where trophoblasts and NK cells appear to play a crucial role through their proven ability to produce growth factors and cytokines that modulate endothelial cell responsiveness. Dendritic cells (DC) are also considered an important regulatory component during pregnancy, mainly due to their role in the establishment of maternal immunologic tolerance. DC are known to increase their numbers at the peri-implantation period in mice, where this accumulation is accompanied by a transitory decrease in the relative number of DC producing the Th2 cytokine interleukin 10 (IL-10). However, the recent finding that DC subsets can promote angiogenesis in a variety of physiopathological settings suggests that the classical functions ascribed to DC during pregnancy need to be revised, as these cells may not only promote immune tolerance but also influence other processes such as decidualization and placentation and the vascular changes associated to them. Thus, by linking immunoregulatory and pro-angiogenic functions, DC may represent a pivotal component of the uterine signaling network involved in the establishment and maintenance of pregnancy. (platform)