mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-DNK-2540mimmun-2540Research ArticleОБЗОРЫREVIEWSДецидуальные естественные киллеры и клетки трофобласта: клеточные, гуморальные и молекулярные механизмы взаимодействияDecidual natural killer cells and trophoblast cells: cellular, humoral and molecular mechanisms of interactionhttps://orcid.org/0000-0002-5229-9732ГребенкинаП. В.GrebenkinaP. V.

Гребенкина Полина Владимировна – лаборант-исследователь лаборатории межклеточных взаимодействий

199034, Санкт-Петербург, Менделеевская линия, 3д.

Grebenkina Polina V., Laboratory Assistant, Laboratory of Intercellular Interactions

199034, St. Petersburg, Mendeleevskaya line, 3d.

grebenkinap@gmail.comhttps://orcid.org/0000-0003-1328-8157МихайловаВ. А.MikhailovaV. A.

Михайлова Валентина Анатольевна – кандидат биологических наук, старший научный сотрудник лаборатории межклеточных взаимодействий ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»; доцент кафедры иммунологии ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФ

Санкт-Петербург

Mikhailova Valentina A., PhD (Biology), Senior Research Associate, Laboratory of Intercellular Interactions, D. Ott Research Institute of Obstetrics, Gynecology and Reproductology; Associate Professor, Department of Immunology, St. Petersburg State I. Pavlov Medical University

St. Petersburg

mva_spb@mail.ruОшколоваА. А.OshkolovaA. A.

Ошколова Арина Андреевна – студент лаборатории межклеточных взаимодействий

Санкт-Петербург

Oshkolova Arina A., Student, Laboratory of Intercellular Interactions

St. Petersburg

aoskolova@gmail.comВершининаС. О.VershininaS. O.

Вершинина Софья Олеговна – студент

Санкт-Петербург

Vershinina Sofia O., Student

St. Petersburg

vershinina@scamt-itmo.ruhttps://orcid.org/0000-0001-8118-9439ДухиноваМ. С.DukhinovaM. S.

Духинова Марина Сергеевна – кандидат биологических наук, ведущий научный сотрудник

Санкт-Петербург

Dukhinova Marina S., PhD (Biology), Leading Research Associate

St. Petersburg

dukhinova@scamt-itmo.ruhttps://orcid.org/0000-0003-4532-7720БаженовД. О.BazhenovD. O.

Баженов Дмитрий Олегович – младший научный сотрудник лаборатории межклеточных взаимодействий

Санкт-Петербург

Bazhenov Dmitriy O., Junior Research Associate, Laboratory of Intercellular Interactions

St. Petersburg

dmitry-bazhenov@mail.ruhttps://orcid.org/0000-0003-1560-7529СельковС. А.SelkovS. A.

Сельков Сергей Алексеевич – доктор медицинских наук, профессор, заслуженный деятель науки РФ, заведующий отделом иммунологии и межклеточных взаимодействий ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»; профессор кафедры иммунологии ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФ

Санкт-Петербург

Selkov Sergey A., PhD, MD (Medicine), Professor, Honoured Science Worker, Head, Department of Immunology and Intercellular Interactions, D. Ott Research Institute of Obstetrics, Gynecology and Reproductology; Professor, Department of Immunology, St. Petersburg State I.Pavlov Medical University

St. Petersburg

selkovsa@mail.ruhttps://orcid.org/0000-0002-5749-2531СоколовД. И.SokolovD. I.

Соколов Дмитрий Игоревич – доктор биологических наук, доцент, заведующий лабораторией межклеточных взаимодействий ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»; профессор кафедры иммунологии ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФ

Санкт-Петербург

Sokolov Dmitriy I., PhD, MD (Biology), Associate Professor, Head, Laboratory of Intercellular Interactions, D. Ott Research Institute of Obstetrics, Gynecology and Reproductology; Professor, Department of Immunology, St. Petersburg State I.Pavlov Medical University

St. Petersburg

falcojugger@yandex.ruФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»РоссияD. Ott Research Institute of Obstetrics, Gynecology and ReproductologyRussian FederationФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»; ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФРоссияD. Ott Research Institute of Obstetrics, Gynecology and Reproductology; First St. Petersburg State I. Pavlov Medical UniversityRussian FederationФГАОУ ВО «Национальный исследовательский университет ИТМО»РоссияNational Research ITMO UniversityRussian Federation20220812202224610851108Copyright © Гребенкина П.В., Михайлова В.А., Ошколова А.А., Вершинина С.О., Духинова М.С., Баженов Д.О., Сельков С.А., Соколов Д.И., 20222022Гребенкина П.В., Михайлова В.А., Ошколова А.А., Вершинина С.О., Духинова М.С., Баженов Д.О., Сельков С.А., Соколов Д.И.Grebenkina P.V., Mikhailova V.A., Oshkolova A.A., Vershinina S.O., Dukhinova M.S., Bazhenov D.O., Selkov S.A., Sokolov D.I.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/2540

Естественные киллеры (NK-клетки) представляют группу лимфоцитов врожденного иммунитета. Помимо NK-клеток периферической крови описаны тканерезидентные популяции. Одной из локальных популяций NK-клеток являются NK-клетки децидуальной оболочки – децидуальные NK-клетки. Децидуальные NK-клетки отличаются по фенотипу и функциям от NK-клеток периферической крови. Эти клетки обладают преимущественно регуляторными свойствами, в то же время они сохраняют способность к реализации цитотоксичности. В матке NK-клетки находятся рядом с клетками плодового происхождения – клетками трофобласта, дифференцирующимися из наружного слоя инвазирующей бластоцисты. Целью обзора явился анализ литературных данных по изучению молекулярных механизмов взаимодействия NK-клеток с клетками трофобласта, а также путей регуляции этих взаимодействий. В обзоре представлены имеющиеся на сегодняшний день данные о рецепторных (как за счет адгезионных молекул, так и цитотоксических рецепторов) и дистантных (с участием цитокинов, хемокинов и ростовых факторов, секретируемых обоими типами клеток) взаимодействиях NK-клеток и клеток трофобласта. Рассмотрены рецепторы, регулирующие контакты NK-клеток и клеток трофобласта с внеклеточным матриксом. В обзоре также представлена информация об активируемых каскадах сигнальных путей в NK-клетках и клетках трофобласта в результате их взаимодействия друг с другом и компонентами внеклеточного матрикса. К настоящему времени молекулярные механизмы регуляции функций NK-клеток и их взаимодействия с клетками трофобласта недостаточно изучены. Авторами предпринята попытка рассмотрения молекулярных механизмов регуляции функциональной активности NK-клеток с участием медиаторного комплекса РНК-полимеразы II. Описано участие комплекса циклин-зависимых киназ CDK8/19, которые входят в состав медиаторного комплекса, в функционировании клеток иммунной системы. Рассмотрены данные об участии CDK8/19 в регуляции внутриклеточных путей сигналинга, а также влияние CDK8/19 на функции NK-клеток. Суммируя представленные в литературе данные, подчеркивается, что при беременности в децидуальной оболочке матки имеет место обширное двустороннее влияние NK-клеток и клеток трофобласта друг на друга, что приводит к изменению фенотипа и функций этих клеток. Перспективным является экспериментальное изучение вклада молекулярных механизмов, вовлеченных в процессы транскрипции и трансляции, в том числе с участием CDK8/19, в биологию NK-клеток, и в поддержание взаимодействия NK-клеток с клетками трофобласта.

Natural killer cells (NK cells) represent a group of lymphocytes of innate immunity. In addition to NK cells of peripheral blood, tissue-resident populations are described. NK cells of the decidual envelope (decidual NK cells) represent one of the local NK cell populations. Decidual NK cells differ in phenotype and function from peripheral blood NK cells. These cells have, mainly, regulatory functions. At the same time they retain the ability to perform cytotoxic effects. In the uterus, NK cells are located closely to the cells of fetal origin, i.e., trophoblast cells, which differentiate from the outer layer of the invading blastocyst. The purpose of the review article was to analyze the literature data on the studies of the molecular interactions between NK cells and trophoblast cells, as well as potential means of regulating these interactions. The review presents currently available data on receptor-mediated effects (due to adhesion molecules and cytotoxic receptors) and distant interactions (involving cytokines, chemokines and growth factors secreted by the both cell types) between NK population and trophoblast cells. The receptors regulating contacts of NK cells and trophoblast cells with extracellular matrix are also considered. The review provides information on activation of signaling pathways in NK cells and trophoblast cells resulting from their interaction with each other and components of the extracellular matrix. Currently, the molecular mechanisms regulating the NK cell functions and their interaction with trophoblast cells have not been studied sufficiently. The authors attempted to consider molecular regulation of the functional activity of NK cells mediated by the molecular complex of RNA polymerase II. We also describe participation of cyclin-dependent CDK8/19 kinases which comprise a part of the mediator complex which provides functioning of immune cells. The data on the participation of CDK8/19 in regulation of intracellular signaling pathways, as well as influence of CDK8/19 on the NK cell functions, are considered. Summarizing the data presented in the literature, one may emphasize that there is an extensive mutual influence of NK cells and trophoblast cells in decidual lining of uterus during pregnancy, thus leading to a changes in phenotype and functions of these cells. Experimental studies are required on the contribution of molecular mechanisms involved in transcription and translation processes to the biology of NK cells, and their role in maintaining interactions between NK cells and trophoblast cells, including the pathways involving CDK8/19.

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