Toll-like receptor signaling in uterine natural killer cells—role in embryonic loss

Embryonic development is a complex process that is regulated by many cell types and signaling pathways. This review focuses on the role of NK cells and regulatory T-cells (Treg cells) in embryonic loss. Approximately 70% of uterine leukocytes until the time of mid-gestation are found to be CD16−CD56bright NK cells. This subset of NK cells, along with Treg cells, has been shown to regulate fetal development. We recently found a population of NK cells in the pregnant mouse uterus with a unique CD3−CD49b+CD25+Foxp3+ phenotype. This review summarizes the studies indicating critical roles for expression of IL-10 by CD3−CD49b+CD25+Foxp3+ cells and CXCR4 expression on CD16−CD56bright NK cells in preventing embryonic loss. In addition, the roles of toll-like receptors (TLRs) and CXCR4 in NK cell migration and functional modulation are discussed.