mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-EOG-2580mimmun-2580Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВлияние гликоделина на CCR6+ субпопуляции T-хелперов, поляризованных в фенотип Th17Effects of glycodelin on CCR6+ cell subpopulations of Th17-polarized helper T cellshttps://orcid.org/0000-0003-4581-1969ТимгановаВ. П.TimganovaV. P.

Тимганова Валерия Павловна – кандидат биологических наук, научный сотрудник лаборатории клеточной иммунологии и нанобиотехнологии.

614081, Пермь, ул. Голева, 13.

Тел.: 8 (342) 280-77-94; Факс: 8 (342) 280-92-11

Valeria P. Timganova - PhD (Biology), Research Associate, Laboratory of Cellular Immunology and Nanobiotechnology, Institute of Ecology and Genetic of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences.

13 Golev St Perm 614081

Phone: +7 (342) 280-77-94; Fax: +7 (342) 280-92-11

timganovavp@gmail.comhttps://orcid.org/0000-0002-6474-1487ЗаморинаС. А.ZamorinaS. A.

Заморина Светлана Анатольевна – доктор биологических наук, ведущий научный сотрудник лаборатории клеточной иммунологии и нанобиотехнологии, ИЭГМ УрО РАН – филиал ФГБУН «ПФИЦ УрО РАН»; профессор кафедры микробиологии и иммунологии ФГАОУ ВО «ПГНИУ».

Пермь

Svetlana A. Zamorina - PhD, MD (Biology), Leading Research Associate, Laboratory of Cellular Immunology and Nanobiotechnology, Institute of Ecology and Genetic of Microorganisms, Perm Federal Research Center, Ural Branch,Russian Academy of Sciences; Professor, Department of Microbiology and Immunology Perm State University.

Perm

mantissa7@mail.ruhttps://orcid.org/0000-0001-5784-6224БочковаМ. С.BochkovaMa. S.

Бочкова Мария Станиславовна – кандидат биологических наук, научный сотрудник лаборатории клеточной иммунологии и нанобиотехнологии, ИЭГМ УрО РАН – филиал ФГБУН «ПФИЦ УрО РАН»; старший преподаватель кафедры микробиологии и иммунологии ФГАОУ ВО «ПГНИУ».

Пермь

Mariya S. Bochkova - PhD (Biology), Research Associate, Laboratory of Cellular Immunology and Nanobiotechnology, Institute of Ecology and Genetic of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences; Senior Lecturer, Department of Microbiology and Immunology Perm State University.

Perm

krasnykh-m@mail.ruhttps://orcid.org/0000-0001-5474-8450ШардинаК. Ю.ShardinaK. Yu.

Шардина Ксения Юрьевна – инженер-исследователь лаборатории клеточной иммунологии и нанобиотехнологии.

Пермь

Kseniya Yu. Shardina - Research Engineer, Laboratory of Cellular Immunology and Nanobiotechnology, Institute of Ecology and Genetic of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences.

Perm

shardinak@gmail.comhttps://orcid.org/0000-0002-6927-1330УжвиюкС. В.UzhviyukS. V.

Ужвиюк Софья Вадимовна – инженер-исследователь лаборатории клеточной иммунологии и нанобиотехнологии.

Пермь

Sofya V. Uzhviyuk - Research Engineer, Laboratory of Cellular Immunology and Nanobiotechnology, Institute of Ecology and Genetic of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences.

Perm

kochurova.sofja@yandex.ruhttps://orcid.org/0000-0001-7068-2789КропаневаМ. Д.KropanevaM. D.

Кропанева Мария Дмитриевна – кандидат биологических наук, младший научный сотрудник лаборатории клеточной иммунологии и нанобиотехнологии, ИЭГМ УрО РАН – филиал ФГБУН «ПФИЦ УрО РАН»; ассистент кафедры микробиологии и иммунологии ФГАОУ ВО «ПГНИУ».

Пермь

Mariya D. Kropaneva - PhD (Biology), Junior Research Associate, Laboratory of Cellular Immunology and Nanobiotechnology, Institute of Ecology and Genetic of Microorganisms, Perm Federal Research Center, Ural Branch,Russian Academy of Sciences; Assistant Professor, Department of Microbiology and Immunology, Perm State University.

Perm

kropanevamasha@gmail.comhttps://orcid.org/0000-0001-6882-4928РаевМ. Б.RayevM. B.

Раев Михаил Борисович – доктор биологических наук, заведующий лабораторией клеточной иммунологии и нанобиотехнологии, ИЭГМ УрО РАН – филиал ФГБУН «ПФИЦ УрО РАН»; профессор кафедры микробиологии и иммунологии ФГАОУ ВО «ПГНИУ».

Пермь

Mikhail B. Rayev - PhD, MD (Biology), Head, Laboratory of Cellular Immunology and Nanobiotechnology, Institute of Ecology and Genetic of Microorganisms, Perm Federal Research Center, Ural Branch,Russian Academy of Sciences; Professor, Department of Microbiology and Immunology Perm State University.

Perm

Mraev@iegm.ruИнститут экологии и генетики микроорганизмов Уральского отделения Российской академии наук – филиал ФГБУН «Пермский федеральный исследовательский центр Уральского отделения Российской академии наук»РоссияInstitute of Ecology and Genetic of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of SciencesRussian FederationИнститут экологии и генетики микроорганизмов Уральского отделения Российской академии наук – филиал ФГБУН «Пермский федеральный исследовательский центр Уральского отделения Российской академии наук»; ФГАОУ ВО «Пермский государственный национальный исследовательский университет»РоссияInstitute of Ecology and Genetic of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences; Perm State UniversityRussian Federation20231710202325613291342Copyright © Тимганова В.П., Заморина С.А., Бочкова М.С., Шардина К.Ю., Ужвиюк С.В., Кропанева М.Д., Раев М.Б., 20232023Тимганова В.П., Заморина С.А., Бочкова М.С., Шардина К.Ю., Ужвиюк С.В., Кропанева М.Д., Раев М.Б.Timganova V.P., Zamorina S.A., Bochkova M.S., Shardina K.Y., Uzhviyuk S.V., Kropaneva M.D., Rayev M.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2580

Гликоделины, белки репродуктивного тракта, отличающиеся гликозилированием и обладающие иммуномодулирующими функциями, представляют интерес в связи с их ролью в формировании иммунной толерантности. Интерлейкин-17-продуцирующие Т-хелперы (Th17), несущие поверхностный маркер CCR6, являются гетерогенной клеточной популяцией с повышенной пластичностью и функциональной дихотомией. С одной стороны, эти клетки поддерживают антимикробный и противогрибковый иммунитет, состав микробиоты, а с другой – участвуют в патогенезе аутоиммунных заболеваний, отторжении трансплантата и осложнениях беременности. Несмотря на достаточно высокий научный интерес к гликоделину как к иммуномодулятору, его прямые эффекты на провоспалительные Th17 не изучались. Поэтому целью нашей работы было исследовать влияние рекомбинантного гликоделина человека на Th17-поляризацию наивных Т-хелперов человека, оценивая экспрессию ими поверхностных молекул CCR6, CCR4 и CXCR3. Наивные Т-хелперы поляризовали в Th17 in vitro при помощи активатора TCR и цитокинов в течение 7 дней с добавлением гликоделина в концентрациях, характерных для первого-второго триместров беременности. После этого определяли процент популяции CD4+CCR6+ клеток (Th17), и ее CCR4+CXCR3-(Th17/Th22) и CCR4-CXC3+ (Th17.1) субпопуляций. Кроме того, при помощи мультиплексного анализа определяли концентрацию цитокинов и хемокинов в супернатантах культур Th17-поляризованных T-хелперов. Рекомбинантный гликоделин в концентрациях, соответствующих таковым при беременности (0,2, 2 и 10 мкг/мл), не изменял процент CD4+CCR6+ клеток в культуре и продукцию ими IL-17 и других исследуемых цитокинов. Однако в концентрации 10 мкг/мл он снижал долю Th17.1 (CCR6+CCR4-CXCR3+) и увеличивал концентрацию IL-2 в культуре Т-хелперов. Помимо этого, установлено, что гликоделин в концентрации 2 мкг/мл проявляет избирательную апоптотическую активность в отношении Th17.1. В силу описанной вовлеченности этих клеток в патологические процессы, данный эффект гликоделина может представлять интерес с точки зрения биофармацевтики, но механизм обнаруженного избирательного действия этого белка беременности требует дальнейшего исследования.

Glycodelins, the glycosylated proteins of reproductive tract are characterized by immunomodulatory functions, are of interest because of their role in the development of immune tolerance. Interleukin-17-producing T helpers (Th17) bearing the surface marker CCR6, are a heterogeneous cell population with increased plasticity and functional dichotomy. On the one hand, these cells support antimicrobial and antifungal immunity and microbiota composition; on the other hand, they are involved in the pathogenesis of autoimmune diseases, graft rejection, and pregnancy complications. Despite the scientific interest in glycodelin as an immunomodulator, its direct effects on pro-inflammatory Th17 have  not been studied. Therefore, the aim of our work was to investigate the effect of recombinant human glycodelin on Th17 polarization of naïve human T helper cells cells by assessing surface expression of CCR6, CCR4, and CXCR3  molecules. Naïve T helper cells were polarized for 7 days in vitro to Th17 cells with a TCR activator and cytokines for 7 days, supplemented with glycodelin at concentrations appropriate for the 1st and 2nd trimesters of pregnancy. The percentages of CD4+CCR6+ cell population (Th17 cells), and their CCR4+CXCR3-(Th17/Th22) and CCR4-CXC3+ subpopulations (Th17.1) was then determined. Moreover, the levels of IL-17, IL-2, and other cytokines/chemokines were determined in the culture supernatants of Th17-polarized T helper cells. Treatment with recombinant glycodelin at concentrations equivalent to those in pregnancy (0.2, 2, and 10 μg/mL) did not alter the percentage of CD4+CCR6+ cells in culture, or their IL-17 production. However,  at a concentration of 10 μg/mL, it caused a decrease in Th17.1 (CCR6+CCR4-CXCR3+) percentage in the T helper culture, and increased the production of IL-2. In addition, glycodelin was found to have selective pro-apoptotic activity against Th17.1 if applied at 2 μg/mL. Given the known involvement of these cells in pathological processes, the observed effect of glycodelin could be of interest from a biopharmaceutical perspective. However, the mechanism of the revealed selective effects of this pregnancy protein needs further investigation.

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The authors declare that there are no conflicts of interest present.