The role of glycodelin in the conversion of Cd11b+ cells to MDSC and the regulation of their functional activity

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Abstract

The amniotic variant of glycodelin (Gd) has pronounced immunomodulatory properties and is involved in the formation of immune tolerance during pregnancy. The role of recombinant Gd at physiological (0.2 and 2 μg/ml) and superphysiological (10 μg/ml) concentrations in regulating the differentiation and functional activity of human myeloid-derived suppressor cells (MDSCs) was investigated in vitro. MDSCs were generated from CD11b+ peripheral blood cells of healthy donors by two-step induction (IL-1β + GM-CSF and then lipopolysaccharide (LPS). The effect of Gd on the content of polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC), intracellular expression of indoleamine 2.3-dioxygenase (IDO), arginase-1 (Arg1, and cytokine profile in cell cultures was investigated. In general, the transformation of CD11b+ cells into MDSCs exhibits the following characteristics: as a result of cytokine induction, predominantly M-MDSCs but no PMN-MDSCs are formed and Arg1 expression is virtually undetected. Gd was found to increase the number of M-MDSCs at concentrations of 2 and 10 μg/ml. Gd was found not to affect Arg1 expression but increased the percentage of MDSCs expressing IDO (10 μg/ml). Gd also modulated the cytokine profile of CD11b+ cells by suppressing the production of IL-19, IL-26 and TWEAK/TNFsF12 at a physiological concentration of 2 μg/ml and the production of IFN-α2 and IL-26 at a supraphysiological concentration. Thus, the role of Gd in the conversion of CD11b+ cells to MDSCs was examined under conditions of cytokine induction in vitro.

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About the authors

K. Yu. Shardina

Institute of Ecology and Genetics of Microorganisms, Ural Division of the Russian Academy of Sciences — Branch of Perm State Research Center, Ural Division of the Russian Academy of Sciences

Author for correspondence.
Email: Shardinak@gmail.com
Russian Federation, Perm

S. A. Zamorina

Institute of Ecology and Genetics of Microorganisms, Ural Division of the Russian Academy of Sciences — Branch of Perm State Research Center, Ural Division of the Russian Academy of Sciences; Perm State National Research University

Email: Shardinak@gmail.com

Биологический факультет 

Russian Federation, Perm; Perm

M. S. Bochkova

Institute of Ecology and Genetics of Microorganisms, Ural Division of the Russian Academy of Sciences — Branch of Perm State Research Center, Ural Division of the Russian Academy of Sciences; Perm State National Research University

Email: Shardinak@gmail.com

Биологический факультет  

Russian Federation, Perm; Perm

V. P. Timganova

Institute of Ecology and Genetics of Microorganisms, Ural Division of the Russian Academy of Sciences — Branch of Perm State Research Center, Ural Division of the Russian Academy of Sciences

Email: Shardinak@gmail.com
Russian Federation, Perm

S. V. Uzhviyuk

Institute of Ecology and Genetics of Microorganisms, Ural Division of the Russian Academy of Sciences — Branch of Perm State Research Center, Ural Division of the Russian Academy of Sciences

Email: Shardinak@gmail.com
Russian Federation, Perm

M. B. Raev

Institute of Ecology and Genetics of Microorganisms, Ural Division of the Russian Academy of Sciences — Branch of Perm State Research Center, Ural Division of the Russian Academy of Sciences; Perm State National Research University

Email: Shardinak@gmail.com

Биологический факультет  

Russian Federation, Perm; Perm

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Supplementary files

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2. Fig. 1. Study of glycodelin (Gd) of different glands for the conversion of CD11b+ cells (from peripheral blood mononuclear cells of donors) to the MDSC phenotype. Medians, interquartile range (Q1–Q3, bar boundaries), minimum and maximum values (vertical bars) are presented; vertical: the proportion of living Lin–HLA-DR‒ cells in the gate; (K1 – control, without adding cytokines and glycodelin to the culture medium, K2 – control 2, adding only cytokines to the medium); differences are significant at P < 0.05: (*) – between K1 and K2 (n = 7, Friedman tests).

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3. Fig. 2. Indoleamine 2,3-dioxygenase (IDO) content in MDSC cells when using glycodelin (Gd) at different concentrations. Medians, interquartile range (Q1–Q3), minimum and maximum values are presented; differences are significant at P < 0.05 (Friedman test): (*) – between the induction control (K1, culture without the addition of cytokines and Gd) and K2 (culture with the addition of cytokines and without Gd); (#) – differences from K2.

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4. Fig. 3. Production of cytokines IFN-α2, IL-19, IL-26 and TWEAK/TNFsF12 by CD11b+ cells induced into the MDSC phenotype using glycodelin (Gd) at different concentrations. The content of cytokines in MDSC culture supernatants is shown. Medians, interquartile range (Q1–Q3, bar boundaries), minimum and maximum values (vertical bars) are presented. (*) – differences in median values (n = 7) are significant at P < 0.05 compared to K2 (culture with the addition of cytokines and without Gd; nonparametric Friedman test).

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