Regulation of kisspeptin-54 activity of indolamine-2,3-dioxygenase and apoptosis of peripheral blood lymphocytes

Abstract

Pregnancy is a phenomenon of natural semi-allogeneic transplantation, since the fetus is half alien due to the expression of paternal antigens. It was found that the hypothalamic hormone kisspeptin during pregnancy is produced by the syncytiotrophoblast of the placenta and participates in the formation of a new specific hormonal background. Several forms of the hormone circulate in the blood of pregnant women: kisspeptin-10, kisspeptin-14 and kisspeptin-54 (according to the number of amino acid residues in the hormone molecule), but the main active form is kisspeptin-54. The main mechanism for the formation of immune tolerance during pregnancy is the induction of the expression of the enzyme indolamine-2,3- dioxygenase (IDO) by antigen-presenting cells of peripheral blood, resulting in the catalysis of tryptophan (Trp) to kynurenins (KYN) blocking the activation and causing apoptosis of cytotoxic CD8+T lymphocytes in the zone of contact of maternal immune cells with placental-fetal complex antigens. In addition, during pregnancy, an important role is assigned to the process of apoptosis, since activated cells can be potentially dangerous for the developing fetus. Immunocompetent blood cells express a specific membrane receptor of kisspeptin (KISS-1R). Since kisspeptin-54 enters the systemic circulation only during pregnancy, the hormone has an effect on immune cells only during this period.The aim of this work was to evaluate the effect of kisspeptin-54 in concentrations comparable to its levelduring physiological pregnancy on IDO activity and apoptosis of peripheral blood lymphocytes.Peripheral blood mononuclear cells (PBMC) obtained from 10 healthy non-pregnant women of reproductive age (from 23 to 32 years) were used as the object of the study. Lymphocyte apoptosis was assessed in PBMC suspension by staining with annexin-V and propidium iodide. The determination of the number of cells in the early and late stages of apoptosis was carried out in the isolated gate of lymphocytes. IDO activity in PBMC was determined spectrophotometrically by changes in the concentration of KYN, the first stable metabolite of the Trp decay pathway.It was found that kisspeptin-54 at a concentration of 4.6 pM corresponding to the second trimester of pregnancy significantly enhances the activity of IDO, increases the number of cells in the early and late stages of apoptosis. Thus, kisspeptin-54 is an important mechanism for controlling these processes during pregnancy, aimed at protecting the semi-allogeneic fetus from adverse immune reactions of the mother and the favorable development of pregnancy.