Background: Background: Analyzing the interaction between natural killer (NK) cells and trophoblast cells is crucial for understanding reproductive immunology processes and developing innovative therapeutic approaches. This study investigates the effects of CDK8/19 kinase inhibition on NK-cell functions and their interactions with trophoblasts, as these kinases regulate immune cell characteristics. Despite active research into kinase inhibitors for disease therapy, their use in modulating maternal-fetal immune interactions remains poorly explored, highlighting the relevance of this work. The aim of the study: The aim of the study was to examine the potential effects of cyclin-dependent kinase inhibitors (CDKIs) on the interaction between NK cells and trophoblasts under conditions mimicking the pregnancy microenvironment. Materials and methods: The study utilized NK-92 and JEG-3 cell lines cultured with cytokines TNFα, IFNγ, TGFβ1, IL-15, IL-18, and IL-10 at concentrations corresponding to human biological fluids. Expression of MICA and NKG2D molecules on NK cells was assessed by flow cytometry after co-culture with trophoblast cells in the presence or absence of cytokine inhibitors, while cytokine levels in supernatants were measured using immunochemical methods. Results: The study demonstrated that CDKI modulates the expression of key molecules such as the activation receptor NKG2D and the stress molecule MICA, and influences the secretion of cytokines, including IL-10 and RANTES. Despite CDKI treatment, trophoblast interaction enhanced NK-cell cytotoxic activity, indicating preserved target recognition mechanisms and confirming the trophoblast's role in regulating NK-cell activity. Differential effects of pro-inflammatory cytokines (IL-18, TNFα, IFNγ) on IL-10 production were observed following CDKI pre-treatment, suggesting potential crosstalk among intracellular signaling pathways. Conclusion: These findings highlight the complex regulation of NK cell-trophoblast interactions and emphasize the need for further research into the use of CDK8/19 inhibitors to modulate immune responses, including applications in reproductive medicine
Background: Background: Analyzing the interaction between natural killer (NK) cells and trophoblast cells is crucial for understanding reproductive immunology processes and developing innovative therapeutic approaches. This study investigates the effects of CDK8/19 kinase inhibition on NK-cell functions and their interactions with trophoblasts, as these kinases regulate immune cell characteristics. Despite active research into kinase inhibitors for disease therapy, their use in modulating maternal-fetal immune interactions remains poorly explored, highlighting the relevance of this work. The aim of the study: The aim of the study was to examine the potential effects of cyclin-dependent kinase inhibitors (CDKIs) on the interaction between NK cells and trophoblasts under conditions mimicking the pregnancy microenvironment. Materials and methods: The study utilized NK-92 and JEG-3 cell lines cultured with cytokines TNFα, IFNγ, TGFβ1, IL-15, IL-18, and IL-10 at concentrations corresponding to human biological fluids. Expression of MICA and NKG2D molecules on NK cells was assessed by flow cytometry after co-culture with trophoblast cells in the presence or absence of cytokine inhibitors, while cytokine levels in supernatants were measured using immunochemical methods. Results: The study demonstrated that CDKI modulates the expression of key molecules such as the activation receptor NKG2D and the stress molecule MICA, and influences the secretion of cytokines, including IL-10 and RANTES. Despite CDKI treatment, trophoblast interaction enhanced NK-cell cytotoxic activity, indicating preserved target recognition mechanisms and confirming the trophoblast's role in regulating NK-cell activity. Differential effects of pro-inflammatory cytokines (IL-18, TNFα, IFNγ) on IL-10 production were observed following CDKI pre-treatment, suggesting potential crosstalk among intracellular signaling pathways. Conclusion: These findings highlight the complex regulation of NK cell-trophoblast interactions and emphasize the need for further research into the use of CDK8/19 inhibitors to modulate immune responses, including applications in reproductive medicine