Role of Kisspeptin and Leptin in the Development of Immune Reactivity during Pregnancy

Abstract

The effects of kisspeptin, an important regulator of reproductive function, and leptin, a classical metabolic hormone, on the formation of inducible regulatory T cells (iTreg) and T helper cells that produce interleukin 17 (Th17), as well as on the activity of indoleamine 2,3-dioxygenase (IDO) have been studied. Both hormones are actively produced by the placenta and involved in the formation of a new hormonal profile during pregnancy. It was found that kisspeptin at concentrations typical for trimesters I–III of pregnancy stimulates the formation of iTreg and simultaneously inhibit Th17 induction. Regardless of the used concentration, kisspeptin increases the secretion of interleukin-10 (IL-10) and reduces the production of IL-17A in CD4⁺ T lymphocytes in women. At the same time leptin at physiological concentrations typical for pregnancy has the opposite effect, inhibiting the formation of iTreg without affecting the production of IL-10 in cultures of CD4⁺T lymphocytes and simultaneous stimulating the induction of Th17 and production of IL-17A in CD4⁺T lymphocytes. At the concentration corresponding to trimesters II–III of pregnancy both hormones significantly enhance lipopolysaccharide-induced activity of IDO in monocytes.