mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2019-1-21-38mimmun-1696Research ArticleОБЗОРЫREVIEWSДИФФЕРЕНЦИРОВКА NK-КЛЕТОК. ВЗГЛЯД ЧЕРЕЗ ПРИЗМУ ТРАНСКРИПЦИОННЫХ ФАКТОРОВ И ВНУТРИКЛЕТОЧНЫХ МЕССЕНДЖЕРОВDIFFERENTIATION OF NK CELLS. A LOOK THROUGH THE PRISM OF TRANSCRIPTION FACTORS AND INTRACELLULAR MESSENGERSМихайловаВ. А.MikhailovaV. A.

к.б.н., старший научный сотрудник лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»; кафедра иммунологии ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова»

199034, Санкт-Петербург, Менделеевская линия, 3. Тел.: 8 (812) 328-98-50

 

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

199034, St. Petersburg, Mendeleev Line, 3. Phone: 7 (812) 328-98-50.

mva_spb@mail.ruБаженовД. О.BazhenovD. O.

младший научный сотрудник лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий 

Санкт-Петербург

Junior Research Associate, Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions

St. Petersburg

БеляковаК. Л.BelyakovaK. L.

младший научный сотрудник лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий 

Санкт-Петербург

Junior Research Associate, Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions

St. Petersburg

СельковС. А.SelkovS. A.

д.м.н., профессор, заслуженный деятель науки, заведующий отделом иммунологии и межклеточных взаимодействий

Санкт-Петербург

PhD, MD (Medicine), Professor, Honored Science Worker, Head, Department of Immunology and Intercellular Interactions

St. Petersburg

СоколовД. И.SokolovD. I.

д.б.н., заведующий лабораторией межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий; кафедра иммунологии; отдел иммунологии 

Санкт-Петербург

PhD, MD (Biology), Head, Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions; Department of Immunology; Department of Immunology

St. Petersburg

ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»; ГБОУ ВПО «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 FederationФГБНУ «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»; ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФ; ФГБНУ «Институт экспериментальной медицины»РоссияD. Ott Research Institute of Obstetrics, Gynecology and Reproductology; First St. Petersburg State I. Pavlov Medical University; Institute of Experimental MedicineRussian Federation2019220120192112138Copyright © Михайлова В.А., Баженов Д.О., Белякова К.Л., Сельков С.А., Соколов Д.И., 20192019Михайлова В.А., Баженов Д.О., Белякова К.Л., Сельков С.А., Соколов Д.И.Mikhailova V.A., Bazhenov D.O., Belyakova K.L., 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/1696

Все лимфоидные клетки относят к врожденному или адаптивному звену иммунитета согласно механизмам реализации иммунных реакций. Реализация функциональной активности NK-клеток не связана с процессами предварительной активации в результате контакта с антигеном, реаранжировкой генов антигенраспознающих рецепторов и клональной пролиферацией. В связи с этим NK-клетки традиционно относят к клеткам врожденного иммунитета. Ранее полагали, что единственной популяцией лимфоидных клеток врожденного иммунитета являются NK-клетки, однако в последние годы в литературе появляется все больше свидетельств существования различных популяций этих клеток, что послужило основанием для выделения общего кластера под названием «лимфоидные клетки врожденного иммунитета» (Innate Lymphoid Cells – ILC). По классификации ILC NK-клетки относят к первой группе врожденных лимфоидных клеток согласно их общим функциональным характеристикам, а также участию транскрипционного фактора T-bet в их дифференцировке. Сложность, многоэтапность и частично нелинейный характер дифференцировки NK-клеток связаны с влиянием клеточного микроокружения, последовательной экспрессией транскрипционных факторов и активацией различных внутриклеточных путей передачи сигнала в NK-клетках. В обзоре рассматривается место NK-клеток в классификации ILC, основные транскрипционные факторы, участвующие в процессе дифференцировки NK-клеток. Авторами предпринимается попытка обобщить основные пути внутриклеточной передачи сигнала в NK-клетках в зависимости от активации цитокинами, присутствующими в клеточном микроокружении и оказывающими влияние на NK-клетки. Особым объектом дифференцировки NK-клеток являются NK-клетки децидуальной оболочки при беременности. Кроме NK-клеток, в составе децидуальной оболочки присутствуют стромальные клетки, клетки трофобласта, макрофаги. В обзоре рассмотрен частный случай влияния клеток микроокружения на экспрессию транскрипционных факторов и активацию внутриклеточных мессенджеров NK-клеток на примере клеток трофобласта. Открытое в настоящее время многообразие NK-клеток, реализующееся в зависимости от микроокружения в процессе их дифференцировки, требует дальнейшего изучения.

All lymphoid cells are referred to as an innate or adaptive immunity unit in terms of the mechanisms of performing immune reactions. The functional activity of natural killer (NK) cells is not associated with pre-activation processes resulting from contact with antigen, rearrangement of antigen-recognition receptor genes, and clonal proliferation. In this regard, NK cells are traditionally referred to as cells of innate immunity. Previously, it was believed that NK cells represent the only population of innate immunity lymphoid cells, but, more recently, there has been increasing evidence in the literature concerning existence of different populations of these cells, thus serving a basis for isolating a common cluster called Innate Lymphoid Cells (ILC). According to the ILC classification, NK cells are classified as the first group of innate lymphoid cells according to their overall functional characteristics, as well as contribution of the T-bet transcription factor to their differentiation. Complexity, multistage and partially nonlinear character of NK cell differentiation are associated with influence of the cellular microenvironment, consistent expression of transcription factors and activation of various intracellular signaling pathways in NK cells. The review considers positioning of NK cells in the ILC classification, the main transcription factors involved in NK cell differentiation. The authors are seeking for generalization of the major routes of intracellular signal transmission in NK cells depending on their activation by cytokines located in the cellular microenvironment and affecting NK cells. The decidual NK cells during pregnancy represent a special object of NK cell differentiation. Stromal cells, trophoblast cells and macrophages are present in the decidua, in addition to NK cells. The review concerns a special case of microenvironmental effects upon expression of transcription factors and activation of NK intracellular messengers, while considering trophoblast cells an example of such influences. The recently discovered variety of NK cells, induced by the microenvironment in the course of their differentiation, requires further study.

NK-клеткилимфоидные клетки врожденного иммунитетадифференцировкатранскрипционные факторывнутриклеточные мессенджерыдецидуальные NK-клеткитрофобластNK cellsinnate immunity lymphocytesdifferentiationtranscription factorsintracellular messengersdecidual NK cellstrophoblastгрант НШ-2873.2018.7.; участие Баженова Д.О. поддержано стипендией Президента РФ СП-2836.2018.4.the grant NSh-2873.2018.7.; the participation of D.O. Bazhenov was supported by a Presidential scholarship of the Russian Federation SP-2836.2018.4.ReferencesAli A.K., Oh J.S., Vivier E., Busslinger M., Lee S.H. NK Cell-specific Gata3 ablation identifies the maturation program required for bone marrow exit and control of proliferation. J. Immunol., 2016, Vol. 196, no. 4, pp. 1753-1767.Ali A.K., Oh J.S., Vivier E., Busslinger M., Lee S.H. NK Cell-specific Gata3 ablation identifies the maturation program required for bone marrow exit and control of proliferation. J. 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The authors declare that there are no conflicts of interest present.