Effect of pregnancy-specific β1-glycoprotein on myeloid-derived suppressor cell differentiation

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population that primarily suppress T lymphocytes in healthy pregnancies and pathologies. MDSCs are one of the key regulators of immune responses. Finding ways to control them is important for the treatment of cancer, autoimmune diseas...

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Main Authors: V. P. Timganova, K. Yu. Shardina, M. S. Bochkova, S. V. Uzhviyuk, D. I. Usanina, S. A. Zamorina
Format: Article
Language:Russian
Published: St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists 2023-06-01
Series:Медицинская иммунология
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Online Access:https://www.mimmun.ru/mimmun/article/view/2838
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author V. P. Timganova
K. Yu. Shardina
M. S. Bochkova
S. V. Uzhviyuk
D. I. Usanina
S. A. Zamorina
author_facet V. P. Timganova
K. Yu. Shardina
M. S. Bochkova
S. V. Uzhviyuk
D. I. Usanina
S. A. Zamorina
author_sort V. P. Timganova
collection DOAJ
description Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population that primarily suppress T lymphocytes in healthy pregnancies and pathologies. MDSCs are one of the key regulators of immune responses. Finding ways to control them is important for the treatment of cancer, autoimmune diseases, miscarriage, and post-transplant complications. The mechanisms of immune suppression by MDSC are: expression of CD73, ADAM17, PD -L1, production of Arg 1, iNOS, IDO, IL -10 and TGF-b1.Pregnancy-specific b1-glycoprotein (PSG) has modulatory effects on dendritic cells and macrophages that mediate the shift of T cell phenotypes toward Th2 and Treg. We have previously shown that native PSG suppresses Th17 differentiation and cytokine production, stimulates the production of IDO by monocytes and the differentiation of Tregs.Considering the immunomodulatory properties of PSG and the key role of MDSCs in pathologies, the aim of our work was to investigate the effect of native and recombinant PSG on the differentiation of MDSCs in vitro.MDSCs were differentiated from CD11b+ peripheral blood cells. Cells were cultured for 7 days and received stepwise GM-CSF, IL-1b, and LPS. Native (n) (1; 10 and 100 mg/mL) and recombinant (r) (1 and 10 mg/mL) PSG were introduced into the cultures three days before the end of incubation. Flow cytometry was used to determine the percentage of MDSC among the cells in culture and the percentage of M-, PMN-, and e-MDSC among the total number of MDSCs.It was found that rPSG (1 mg/mL) increased the percentage of MDSCs in culture. Both nPSG (1 and 10 mg/mL) and rPSG (10 mg/mL) increased the proportion of M-MDSC, whereas rPSG (10 mg/mL) decreased the number of PMN-MDSC.Thus, the cytokine background in CD11b+ cell cultures favored the differentiation of predominantly M-MDSC, similar to the tumor microenvironment, whereas native and recombinant PSG enhanced this effect. Thus, nPSG and rPSG are able to modulate the differentiation of MDSCs by increasing their number, mainly due to the monocytic subpopulation. This fact opens perspectives for new research on targeted manipulation of MDSCs.
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spelling doaj-art-13b45f1f6bbe4fd482b77089135033802025-08-20T03:37:57ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2023-06-0125351352010.15789/1563-0625-EOP-28381691Effect of pregnancy-specific β1-glycoprotein on myeloid-derived suppressor cell differentiationV. P. Timganova0K. Yu. Shardina1M. S. Bochkova2S. V. Uzhviyuk3D. I. Usanina4S. A. Zamorina5Institute of Ecology and Genetics of Microorganisms, Branch of the Perm Federal Research Center, Ural Branch, Russian Academy of SciencesInstitute of Ecology and Genetics of Microorganisms, Branch of the Perm Federal Research Center, Ural Branch, Russian Academy of SciencesInstitute of Ecology and Genetics of Microorganisms, Branch of the Perm Federal Research Center, Ural Branch, Russian Academy of SciencesInstitute of Ecology and Genetics of Microorganisms, Branch of the Perm Federal Research Center, Ural Branch, Russian Academy of SciencesInstitute of Ecology and Genetics of Microorganisms, Branch of the Perm Federal Research Center, Ural Branch, Russian Academy of SciencesInstitute of Ecology and Genetics of Microorganisms, Branch of the Perm Federal Research Center, Ural Branch, Russian Academy of SciencesMyeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population that primarily suppress T lymphocytes in healthy pregnancies and pathologies. MDSCs are one of the key regulators of immune responses. Finding ways to control them is important for the treatment of cancer, autoimmune diseases, miscarriage, and post-transplant complications. The mechanisms of immune suppression by MDSC are: expression of CD73, ADAM17, PD -L1, production of Arg 1, iNOS, IDO, IL -10 and TGF-b1.Pregnancy-specific b1-glycoprotein (PSG) has modulatory effects on dendritic cells and macrophages that mediate the shift of T cell phenotypes toward Th2 and Treg. We have previously shown that native PSG suppresses Th17 differentiation and cytokine production, stimulates the production of IDO by monocytes and the differentiation of Tregs.Considering the immunomodulatory properties of PSG and the key role of MDSCs in pathologies, the aim of our work was to investigate the effect of native and recombinant PSG on the differentiation of MDSCs in vitro.MDSCs were differentiated from CD11b+ peripheral blood cells. Cells were cultured for 7 days and received stepwise GM-CSF, IL-1b, and LPS. Native (n) (1; 10 and 100 mg/mL) and recombinant (r) (1 and 10 mg/mL) PSG were introduced into the cultures three days before the end of incubation. Flow cytometry was used to determine the percentage of MDSC among the cells in culture and the percentage of M-, PMN-, and e-MDSC among the total number of MDSCs.It was found that rPSG (1 mg/mL) increased the percentage of MDSCs in culture. Both nPSG (1 and 10 mg/mL) and rPSG (10 mg/mL) increased the proportion of M-MDSC, whereas rPSG (10 mg/mL) decreased the number of PMN-MDSC.Thus, the cytokine background in CD11b+ cell cultures favored the differentiation of predominantly M-MDSC, similar to the tumor microenvironment, whereas native and recombinant PSG enhanced this effect. Thus, nPSG and rPSG are able to modulate the differentiation of MDSCs by increasing their number, mainly due to the monocytic subpopulation. This fact opens perspectives for new research on targeted manipulation of MDSCs.https://www.mimmun.ru/mimmun/article/view/2838myeloid-derived suppressor cellsimmunosuppressionpregnancy-specific β1-glycoproteincd11b+cd33+ cellsm-mdscpmn-mdsc
spellingShingle V. P. Timganova
K. Yu. Shardina
M. S. Bochkova
S. V. Uzhviyuk
D. I. Usanina
S. A. Zamorina
Effect of pregnancy-specific β1-glycoprotein on myeloid-derived suppressor cell differentiation
Медицинская иммунология
myeloid-derived suppressor cells
immunosuppression
pregnancy-specific β1-glycoprotein
cd11b+cd33+ cells
m-mdsc
pmn-mdsc
title Effect of pregnancy-specific β1-glycoprotein on myeloid-derived suppressor cell differentiation
title_full Effect of pregnancy-specific β1-glycoprotein on myeloid-derived suppressor cell differentiation
title_fullStr Effect of pregnancy-specific β1-glycoprotein on myeloid-derived suppressor cell differentiation
title_full_unstemmed Effect of pregnancy-specific β1-glycoprotein on myeloid-derived suppressor cell differentiation
title_short Effect of pregnancy-specific β1-glycoprotein on myeloid-derived suppressor cell differentiation
title_sort effect of pregnancy specific β1 glycoprotein on myeloid derived suppressor cell differentiation
topic myeloid-derived suppressor cells
immunosuppression
pregnancy-specific β1-glycoprotein
cd11b+cd33+ cells
m-mdsc
pmn-mdsc
url https://www.mimmun.ru/mimmun/article/view/2838
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