Cell and Tissue BiologyCell and Tissue BiologyЦитология0041-37713034-6061The Russian Academy of Sciences66961010.31857/S0041377124020027RKMDZWArticlesСтатьиResearch ArticleThe role of glycodelin in the conversion of Cd11b+ cells to MDSC and the regulation of their functional activityРоль гликоделина в конверсии CD11b+-клеток в MDSC и регуляции их функциональной активностиShardinaK. Yu.ШардинаК. Ю.
Russian Federation
Shardinak@gmail.comZamorinaS. A.ЗаморинаС. А.
Russian Federation

Биологический факультет

Shardinak@gmail.comBochkovaM. S.БочковаМ. С.
Russian Federation

Биологический факультет

Shardinak@gmail.comTimganovaV. P.ТимгановаВ. П.
Russian Federation
Shardinak@gmail.comUzhviyukS. V.УжвиюкС. В.
Russian Federation
Shardinak@gmail.comRaevM. B.РаевМ. Б.
Russian Federation

Биологический факультет

Shardinak@gmail.comInstitute 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 SciencesИнститут экологии и генетики микроорганизмов Уральского отделения Российской академии наук – филиал Пермского федерального исследовательского центра Уральского отделения РАНPerm State National Research UniversityПермский государственный национальный исследовательский университет1503202466212213027022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0041-3771/article/view/669610

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.

Гликоделин (Gd) обладает выраженными иммуномодулирующими свойствами, участвуя в формировании иммунной толерантности в период беременности. Исследовали роль рекомбинантного Gd в физиологических (0.2 и 2 мкг/мл) и сверхфизиологической (10 мкг/мл) концентрациях в регуляции дифференцировки и функциональной активности миелоидных супрессорных клеток человека (myeloid-derived suppressor cells, MDSC) в условиях in vitro. MDSC генерировали из CD11b+-клеток периферической крови здоровых доноров двухэтапной индукцией (IL-1β + GM-CSF и липополисахарид). Оценивали влияние Gd на уровень полиморфноядерных MDSC (PMN-MDSC) и моноцитарных MDSC (M-MDSC), измеряли внутриклеточный уровень индоламин-2,3-диоксигеназы (IDO), аргиназы-1 (Arg1) и цитокиновый профиль в культурах этих клеток. В целом конверсия CD11b+-клеток в MDSC имеет следующие особенности: в результате цитокиновой индукции генерируются преимущественно M-MDSC, но не PMN-MDSC, и практически не детектируется уровень Arg1. Установлено, что Gd повышал количество M-MDSC в концентрациях 2 и 10 мкг/мл. Показано, что Gd не влиял на содержание Arg1, но повышал долю MDSC, экспрессирующих IDO (10 мкг/мл). Gd также модулировал цитокиновый профиль CD11b+-клеток (в физиологической концентрации 2 мкг/мл), подавляя продукцию IL-19, IL-26 и TWEAK/ TNFsF12, а в сверхфизиологической концентрации – продукцию IFN-α2 и IL-26.

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