The prospects of regulating the interaction between NK cells and trophoblast cells through cyclin-dependent kinase inhibitors
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
Grebenkina PV, Tyshchuk EV, Marko OB, et al. The prospects of regulating the interaction between NK cells and trophoblast cells through cyclin-dependent kinase inhibitors. Research Results in Biomedicine. 2026;12(2):316-333. Russian. DOI: 10.18413/2658-6533-2026-12-2-0-9
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