mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2017-4-359-374mimmun-1308Research ArticleОБЗОРЫREVIEWSМОЛЕКУЛЯРНО-КЛЕТОЧНЫЕ МЕХАНИЗМЫ, ОПОСРЕДУЕМЫЕ ДЕНДРИТНЫМИ КЛЕТКАМИ, УЧАСТВУЮЩИЕ В ИНДУКЦИИ ТОЛЕРАНТНОСТИMOLECULAR AND CELLULAR MECHANISMS MEDIATED BY DENDRITIC CELLS INVOLVED IN THE INDUCTION OF TOLERANCEСенниковС. В.SennikovS. V.

Сенников Сергей Витальевич – доктор медицинских наук, профессор, заведующий лабораторией молекулярной  иммунологии.

630099, Новосибирск, ул. Ядринцевская, 14, ком. 301-309, тел.: 8 (383) 222-19-10, факс: 8 (383) 222-70-28

Sennikov  Sergey V. - PhD, MD (Medicine), Professor, Head, Laboratory of Molecular Immunology.

630099, Novosibirsk, Yandrintsevskaya str., 14, room 301-309. Phone: 7 (383) 222-19-10. Fax: 7 (383) 222-70-28

sennikovsv@gmail.comКуликоваЕ. В.KulikovaE. V.

Кандидат биологических наук, научный сотрудник лаборатории молекулярной  иммунологии.

Новосибирск

PhD (Biology), Research Associate, Laboratory of Molecular Immunology.

Novosibirsk

КнауэрН. Ю.KnauerN. Yu.

Младший научный сотрудник лаборатории клинической иммунопатологии.

Новосибирск

Junior Research Associate, Laboratory of Clinical Immunopathology.

Novosibirsk

ХантаковаЮ. Н.KhantakovaYu. N.

Кандидат медицинских наук, научный сотрудник лаборатории молекулярной  иммунологии.

Новосибирск

PhD (Medicine), Research Associate, Laboratory of Molecular Immunology.

Novosibirsk 

ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии»РоссияResearch Institute of Fundamental and Clinical ImmunologyRussian Federation201730082017194359374Copyright © Сенников С.В., Куликова Е.В., Кнауэр Н.Ю., Хантакова Ю.Н., 20172017Сенников С.В., Куликова Е.В., Кнауэр Н.Ю., Хантакова Ю.Н.Sennikov S.V., Kulikova E.V., Knauer N.Y., Khantakova Y.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1308

Аутоиммунные заболевания и осложнения после  трансплантационных операций являются серьезной проблемой здравоохранения, так как  зачастую приводят к ухудшению качества жизни, снижению трудоспособности и инвалидизации населения. На сегодняшний день многообещающим методом терапии данных состояний  является индукция  антиген-специфической  толерантности, в процессе формирования которой важное место  занимают дендритные клетки. В данном обзоре проведен анализ современных данных по характеристике толерогенных дендритных клеток, по факторам, индуцирующим толерогенные свойства у дендритных клеток, по развитию центральной и периферической толерантности посредством дендритных клеток, по  роли  толерогенных дендритных клеток в формировании В-регуляторных клеток, а также  по  молекулярно-клеточным механизмам, которые принимают участие  в формировании иммунологической толерантности, зависимой от толерогенных дендритных клеток. Толерогенные дендритные клетки играют  ведущую  роль в поддержании  иммунного гомеостаза путем  индукции иммунологической толерантности, механизмы которой связаны с генерацией Т-регуляторных клеток, индукцией анергии или  апоптоза Т-клеток. Формирование толерогенных свойств у дендритных клеток происходит под влиянием различных факторов, регулирующих созревание  и  дифференцировку дендритных клеток и  индуцирующих синтез ими противовоспалительных агентов. Благодаря своей  способности индуцировать натуральные и периферические Т-регуляторные клетки, дендритные клетки вносят свой  вклад  в развитие центральной и периферической толерантности в организме. Анализ результатов экспериментальных  работ  свидетельствует о том,  что помимо индукции Т-регуляторных клеток толерогенные дендритные клетки принимают участие  в генерации В-регуляторных клеток, которые играют  не последнюю роль в формировании толерантности и имеют  способность влиять на популяцию Т-регуляторных клеток. Однако механизмы, которые приводят к формированию популяции В-регуляторных клеток под действием толерогенных дендритных клеток, не вполне установлены. Обзор  литературных данных показал, что молекулярно-клеточные механизмы индукции иммунологической толерантности посредством толерогенных дендритных клеток и других субпопуляций регуляторных клеток, взаимодействующих друг с другом,  во многом схожи. На сегодняшний день роль толерогенных дендритных клеток в поддержании иммунологической толерантности в целом определена, однако некоторые аспекты требуют более глубокого изучения. Последующие экспериментальные исследования приведут к лучшему пониманию механизмов сигнализации и реализации иммунологических функций толерогенных дендритных клеток, что предоставит дополнительную информацию для разработки подходов применения толерогенных дендритных клеток для контроля аутоиммунных заболеваний и трансплантационных осложнений.

Autoimmune diseases  and  complications  after  transplantation  operations are  major   public health  problem, as they often  lead to deterioration in the quality  of life, reduce  work capacity  and  disability in the  population. To date, the  induction of antigen-specific tolerance is the  promising method of therapy. During this process dendritic cells play important role.  In  this review current data  of tolerogenic dendritic cells characterization, of factors inducing tolerogenic properties in dendritic cells, development of central  and peripheral tolerance by dendritic cells, role of tolerogenic dendritic cells in the formation of regulatory B cells, molecular and cellular mechanisms that are involved in the formation of an immunological tolerance depending on tolerogenic dendritic cells were analyzed. Tolerogenic dendritic cells play a key role in maintaining of immune homeostasis by inducing immunological tolerance mechanisms which  are associated with the  generation of regulatory T cells, induction of anergy or apoptosis of T cells. Formation of tolerogenic properties in dendritic cells is occurred by various factors that regulate the maturation and differentiation of dendritic cells and induce anti-inflammatory agents synthesis of them. Because of their ability to induce natural and peripheral regulatory T cells, dendritic cells contribute to the development of the central  and peripheral tolerance in the organism. Analysis of the results  of experimental work demonstrates that  in addition to induction of regulatory T cells tolerogenic dendritic cells participate in generating of regulatory B cells that  play a role in the  formation of tolerance and  have the  ability  to affect  the  population of regulatory T cells. However, the  mechanisms that lead to the formation of B cell population by tolerogenic dendritic cells have not been completely established yet. Review of published data showed that the molecular and cellular mechanisms of immunological tolerance induction by tolerogenic dendritic cells and other regulatory cell subpopulations interacting with each other are similar to a large extent.  Currently, the role of tolerogenic dendritic cells in maintaining of immune tolerance is determined generally, however, some aspects  require  further  investigation. Subsequent experimental studies will lead to a better understanding of the signaling mechanisms and the realization of immunological functions of tolerogenic dendritic cells, which provide additional information for application approaches development of tolerogenic dendritic cells for the control of autoimmune diseases and transplant complications.

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