Natural killer cells in recurrent miscarriage: An overview

•NK cells play a physiological role in pregnancy.•NK cells in women with recurrent miscarriages exhibit a more activated state.•High production of pro-inflammatory cytokines by NK cells in women with recurrent miscarriages.•The role of NK cells in recurrent miscarriage is still under debate. Recurrent Miscarriage is an early pregnancy complication which affects about 1–3 % of child-bearing couples. The mechanisms involved in the occurrence of recurrent miscarriages are not clearly understood. In the last decade Natural Killer cells have been studied in peripheral blood and uterus in order to determine if there are specific characteristics of Natural Killer cells associated with miscarriage. Different authors have described an increased number of uterine and peripheral blood Natural Killer cells in women with recurrent miscarriages compared to control women. However, its relationship with miscarriage has not been confirmed. In patients with recurrent miscarriage a lack of inhibition of decidua Natural Killer cells can be observed, which leads to a more activated state characterized by higher levels of proinflammatory cytokines. In peripheral blood, it has been also reported a dysfunctional cytokine production by Natural Killer cells, with an increase of interferon-γ levels and a decrease of Interleukin-4. Significant progress has been made in the last decade in understanding the biology of Natural Killer cells, including the identification of new receptors that also contribute to the activation and regulation of Natural Killer cells. In this review, we summarize the current progress in the study of Natural Killer cells in recurrent miscarriage.