The effect of pregnancy-specific β1-glycoprotein on PD-L1 and CD73 expression by myeloid-derived suppressor cells and their cytokine profile

Myeloid-derived suppressor cells (MDSC) play a crucial role in establishing immune tolerance, including during pregnancy, due to their ability to suppress immune responses through various mechanisms. One of the key regulators of the immune system during gestation is pregnancy-specific β1-glycoprotein (PSG), which possesses pronounced immunosuppressive properties. The aim of this study was to investigate the effects of native and recombinant PSG on the functional activity of MDSC derived from the peripheral blood of healthy donors. For this purpose, CD11b+ cells were isolated by immunomagnetic separation and differentiated into MDSC using GM-CSF, IL-1β, and LPS. Various concentrations of native (1, 10, and 100 μg/mL) and recombinant (1 and 10 μg/mL) PSG were applied in the experiments. Cell phenotyping was performed by flow cytometry to assess the expression of PD-L1 and CD73, while inducible nitric oxide synthase (iNOS) levels were measured, and a cytokine profile comprising 17 markers was analyzed using multiplex assays. It was found that recombinant PSG at 1 μg/mL significantly increased PD-L1 expression on MDSC, and at 10 μg/mL elevated CD73 levels, whereas native PSG had no significant effect on these markers. Neither form of PSG influenced iNOS production; however, recombinant PSG (10 μg/mL) reduced the level of the chemokine MIP-1β without altering the production of other cytokines studied. These results suggest that recombinant PSG may enhance the immunosuppressive potential of MDSCs by increasing PD-L1 and CD73 expression and suppressing MIP-1β production, which may be important for the development of new biopharmaceutical strategies for modulating immune responses in autoimmune diseases and transplantation. The selective effects of recombinant PSG on MDSC functions are likely related to its structural features, including post-translational modifications.