Abstract <p>Myeloid-derived suppressor cells (MDSC) play a key role in the formation of immune tolerance, including during pregnancy, due to their ability to suppress the immune response using various mechanisms. One of the important regulators of the immune system during gestation is pregnancy specific glycoprotein (PSG), which has pronounced immunosuppressive properties. The aim of this study was to investigate the effect of native and recombinant PSG on the functional activity of MDSC obtained from the peripheral blood of healthy donors. For this purpose, CD11b+ cells were isolated by immunomagnetic separation and differentiated into MDSCs using GM-CSF, IL-1β, and lipopolysaccharide (LPS). Physiological concentrations of native (1, 10, 100 μg/mL) and recombinant (1, 10 μg/mL) PSG were used in the experiment. Cell phenotyping was performed by flow cytometry with determination of PD-L1 and CD73 membrane proteins, as well as measurement of inducible NO synthase (iNOS) levels and analysis of the cytokine profile (17 markers) using multiplex analysis. It was found that recombinant PSG at a concentration of 1 μg/mL significantly increased the density of PD-L1 protein on the surface of MDSC, and at a concentration of 10 μg/mL increased the level of CD73, while native PSG had no significant effect on these parameters. Both variants of PSG did not affect iNOS production, but recombinant PSG (10 μg/mL) reduced the level of MIP-1β chemokine without altering the production of other cytokines studied. The results obtained indicate that recombinant PSG can enhance the immunosuppressive potential of MDSC by increasing the membrane molecules PD-L1 and CD73, as well as suppressing MIP-1β production, which may be important for the development of new bio-pharmacological approaches to correcting the immune response in autoimmune diseases and transplantation. The structural features of recombinant PSG associated with post-translational modifications probably determine its selective effect on the functional properties of MDSC.</p>

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The Effect of Pregnancy Specific Glycoprotein on the Presence of PD-L1 and CD73 Membrane Molecules on Myeloid-Derived Suppressor Cells and Their Cytokine Profile

  • K. Yu. Shardina,
  • V. P. Timganova,
  • D. I. Usanina,
  • M. S. Bochkova,
  • S. A. Zamorina

摘要

Abstract

Myeloid-derived suppressor cells (MDSC) play a key role in the formation of immune tolerance, including during pregnancy, due to their ability to suppress the immune response using various mechanisms. One of the important regulators of the immune system during gestation is pregnancy specific glycoprotein (PSG), which has pronounced immunosuppressive properties. The aim of this study was to investigate the effect of native and recombinant PSG on the functional activity of MDSC obtained from the peripheral blood of healthy donors. For this purpose, CD11b+ cells were isolated by immunomagnetic separation and differentiated into MDSCs using GM-CSF, IL-1β, and lipopolysaccharide (LPS). Physiological concentrations of native (1, 10, 100 μg/mL) and recombinant (1, 10 μg/mL) PSG were used in the experiment. Cell phenotyping was performed by flow cytometry with determination of PD-L1 and CD73 membrane proteins, as well as measurement of inducible NO synthase (iNOS) levels and analysis of the cytokine profile (17 markers) using multiplex analysis. It was found that recombinant PSG at a concentration of 1 μg/mL significantly increased the density of PD-L1 protein on the surface of MDSC, and at a concentration of 10 μg/mL increased the level of CD73, while native PSG had no significant effect on these parameters. Both variants of PSG did not affect iNOS production, but recombinant PSG (10 μg/mL) reduced the level of MIP-1β chemokine without altering the production of other cytokines studied. The results obtained indicate that recombinant PSG can enhance the immunosuppressive potential of MDSC by increasing the membrane molecules PD-L1 and CD73, as well as suppressing MIP-1β production, which may be important for the development of new bio-pharmacological approaches to correcting the immune response in autoimmune diseases and transplantation. The structural features of recombinant PSG associated with post-translational modifications probably determine its selective effect on the functional properties of MDSC.