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

Q4 Biochemistry, Genetics and Molecular Biology Cell and Tissue Biology Pub Date : 2024-08-06 DOI:10.1134/s1990519x24700342

K. Yu. Shardina, S. A. Zamorina, M. S. Bochkova, V. P. Timganova, S. V. Uzhviyuk, M. B. Raev

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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.

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甘氨蝶呤在 CD11b+ 细胞转化为 MDSCs 及其功能活性调控中的作用

摘要甘油三酯（Gd）具有明显的免疫调节特性，并参与妊娠期免疫耐受的形成。本研究在体外研究了生理浓度（0.2 和 2 μg/mL）和超生理浓度（10 μg/mL）的重组 Gd 对人髓源性抑制细胞（MDSCs）分化和功能活性的调节作用。通过两步诱导（IL-1β + 粒细胞-单核细胞集落刺激因子（GM-CSF）和脂多糖）从健康供体的外周血 CD11b+ 细胞中获得 MDSCs。评估了 Gd 对多形核 MDSCs（PMN-MDSCs）和单核 MDSCs（M-MDSCs）水平的影响。对这些细胞培养物中吲哚胺 2,3-二氧化酶（IDO）和精氨酸酶 1（Arg1）的细胞内水平以及细胞因子谱进行了测定。一般来说，CD11b+细胞向MDSCs的转化具有以下特点：由于细胞因子的诱导，主要生成M-MDSCs，而不是PMN-MDSCs，而且几乎检测不到Arg1的水平。研究发现，浓度为 2 和 10 μg/mL 的钆能增加 M-MDSCs 的数量。研究表明，Gd 不会影响 Arg1 的含量，但会增加表达 IDO（10 μg/mL）的 MDSC 数量。钆还调节了CD11b+细胞的细胞因子谱（生理浓度为2微克/毫升），抑制了IL-19、IL-26和TWEAK/TNFsF12的产生，在超生理浓度下，抑制了IFN-α2和IL-26的产生。

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来源期刊

Cell and Tissue Biology Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

0.80

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期刊介绍： The journal publishes papers on vast aspects of cell research, including morphology, biochemistry, biophysics, genetics, molecular biology, immunology. The journal accepts original experimental studies, theoretical articles suggesting novel principles and approaches, presentations of new hypotheses, reviews highlighting major developments in cell biology, discussions. The main objective of the journal is to provide a competent representation and integration of research made on cells (animal and plant cells, both in vivo and in cell culture) offering insight into the structure and functions of live cells as a whole. Characteristically, the journal publishes articles on biology of free-living and parasitic protists, which, unlike Metazoa, are eukaryotic organisms at the cellular level of organization.