Hormone-Dependent Reprogramming of NK Cell Functions in the Aspect of Pregnancy

Abstract

Natural killer (NK) lymphocytes belong to the innate lymphoid cells, which have a cytotoxic effect on target cells and are capable of producing a large number of regulatory factors (cytokines, chemokines). During pregnancy, the peripheral blood CD56brightCD16-NK cells migrate to the uterus and transform into decidual (d)NK cells. dNK have a tolerant phenotype and play a leading role in the regulation of invasive syncytiotrophoblast growth and provide peripheral immune tolerance in the area of utero-placental contact. However, the mechanisms of the NK phenotype shift from cytotoxic towards the tolerant remain poorly understood. Hormones are physiological inducers of peripheral immune tolerance and modulate the functions of peripheral blood NK at pregnancy. The most physiologically important are hormones that appear in the woman body only during pregnancy (estriol) and whose levels are considerably increases during pregnancy due to placental synthesis (leptin, ghrelin and kisspeptin). New physiological mechanisms of endocrine control of NK cells of the immune maternal systems are represented in this review. The reproductive hormone effects on NK phenotype changes, secretory and cytotoxic potential, cytokine production and miRNAs-dependent regulation mechanisms are analyzed. Hormone-dependent regulation of the inhibitory molecule expressions, cytokine productions, cytotoxic potential of NK cells promotes the NK phenotype shift from cytotoxic towards regulatory at pregnancy. The hormone regulation of miRNAs plays a pivotal role in driving immune functions of NK. Hormone-dependent regulation of NK are promising for understanding the mechanisms underlying spontaneous abortions and the escape of cancer cells from the immune system.