Molecular Mechanisms of the Regulation by Kisspeptin of the Formation and Functional Activity of Treg and Th17

We investigated molecular mechanisms of the immunomodulatory effects of hormone kisspeptin on the formation and functional activity of inducible regulatory T cells (iTreg) and lymphocytes T helpers-17 (Th17), using inhibitory analysis and direct measurements of the intracellular cAMP level. It was established that kisspeptin in concentrations typical of II and III trimester of pregnancy, increases the iTreg formation and simultaneously inhibits the induction of Th17. Regardless of the concentration used, the hormone increased the IL-10 production and decreased IL-17A by CD4(+)T lymphocytes of women. Correlation analysis revealed a statistically significant negative relationship between the number of iTreg and Th17 and between the IL-10 and IL-17A levels under the influence kisspeptin in a concentration of 9.6 pmol/L. In addition, a significant positive correlation was found between the number of iTreg and levels of IL-10 produced by CD4(+)T lymphocytes of women under the influence of kisspeptin. It was established that implementation of the kisspeptin immunomodulatory effects is associated with increased levels of cAMP and depends on the activity of the protein binding cAMP-responsive element (CREB) and kinase MAPK/ERK (MEK 1/2). A direct correlation between increased levels of cAMP and the number iTreg was found.