Natural killer cells in human pregnancy.

While conventional NK cells play an important role in early defenses against pathogens thanks to their cytolytic activity and production of pro-inflammatory chemokines and cytokines, those present in decidua (dNK cells), during early pregnancy, are primarily involved in tissue building and remodeling and in the formation of new blood vessels. This occurs mainly via the release of IL-8, VEGF, SDF-1 and IP-10. In addition, we show that by interacting with particular myelomonocytic cells (dCD14(+)) they contribute to the induction of regulatory T cells (Tregs). In turn, Tregs are thought to play a pivotal role in immunosuppression and induction of tolerance toward the fetal allograft. We recently demonstrated that CD34(+) hematopoietic precursors (dCD34(+)) are present in decidual tissues, thus suggesting that dNK cells might derive from such precursors. Indeed, this was confined by in vitro experiments in which dCD34(+) cells differentiated into dNK cells upon culture with appropriate cytokine combinations or even in co-culture with decidua-derived stromal cells (dSC). It is possible to speculate that inappropriate cellular interactions in the decidual microenvironment or defects of dNK (or dCD14(+)) cell generation might negatively influence pregnancy success.