The Role of Clycodelin in Conversion of CD11b+ Cells to MDSCs and Regulation of Their Functional Activity

Abstract

Glycodelin (Gd) has pronounced immunomodulatory properties and participates in the development of immune tolerance during pregnancy. The role of recombinant Gd in physiological (0.2 and 2 μg/mL) and superphysiological (10 μg/mL) concentrations in the regulation of differentiation and functional activity of human myeloid-derived suppressor cells (MDSCs) was investigated in vitro. MDSCs were obtained from peripheral blood CD11b⁺ cells of healthy donors by two-step induction (IL-1β + granulocyte–monocyte colony-stimulating factor (GM-CSF) and lipopolysaccharide). The effect of Gd on the level of polymorphonuclear MDSCs (PMN-MDSCs) and monocyte MDSCs (M-MDSCs) was assessed. The intracellular level of indoleamine 2,3-dioxygenase (IDO) and arginase 1 (Arg1), as well as the cytokine profile in cultures of these cells, was measured. In general, the conversion of CD11b⁺ cells into MDSCs has the following features: as a result of cytokine induction, predominantly M-MDSCs are generated, but not PMN-MDSCs, and the level of Arg1 is practically not detected. It was found that Gd increased the number of M-MDSCs at concentrations of 2 and 10 μg/mL. It was shown that Gd did not affect the content of Arg1, but increased the number of MDSCs expressing IDO (10 μg/mL). Gd also modulated the cytokine profile of CD11b⁺ cells (at a physiological concentration of 2 μg/mL), suppressing IL-19, IL-26, and TWEAK/TNFsF12 production and, at a supraphysiological concentration, the production of IFN-α2 and IL-26.