Apoptotic Receptors and CD107a Expression by NK Cells in an Interaction Model with Trophoblast Cells

Area of Science:

• Immunology
• Reproductive Biology
• Cell Biology

Background:

• Natural killer (NK) cells play a crucial role in cytotoxicity, utilizing ligands like TRAIL and FasL, but are also susceptible to apoptosis via TRAIL receptors.
• Uterine NK cells interact with fetal trophoblasts, a critical interaction in pregnancy, where NK cell cytotoxicity towards trophoblasts is a key consideration.

Purpose of the Study:

• To investigate the expression of proapoptotic receptors and ligands on NK cells during interaction with trophoblast cells.
• To determine the impact of cytokines and chorionic villi factors on NK cell apoptosis receptor expression and function.

Main Methods:

• Utilized the NK-92 cell line as NK cells and the JEG-3 cell line as trophoblast target cells.
• Applied various cytokines (IL-1β, IL-15, IL-18, TNFα, IL-10, TGFβ) and conditioned media from chorionic villi explants as inducers.
• Assessed the expression of apoptotic receptors (DR4, DR5, DcR1) and ligands (TRAIL, FasL) on NK cells via flow cytometry.

Main Results:

• Cytokines TNFα and TGFβ modulated NK cell apoptotic receptor expression, increasing Fas and decreasing DR5, respectively.
• Soluble chorionic villi factors altered TRAIL and FasL expression, suggesting differential regulation of apoptosis mechanisms across trimesters.
• Trophoblast cells and chorionic villi factors reduced NK cell expression of TRAIL, DcR1, DR4, and DR5, indicating trophoblast-mediated inhibition of NK cell cytotoxicity.

Conclusions:

• Soluble factors from chorionic villi regulate NK cell resistance to apoptosis, likely by binding TRAIL and maintaining NK cell activity.
• Trophoblast cells appear to exert an inhibitory effect on NK cell cytotoxicity, modulating key apoptosis-related molecules.
• This study elucidates mechanisms by which NK cell activity is regulated in the context of trophoblast interaction, relevant to pregnancy immunology.