Аннотация
Цель обзора – обобщить данные о роли интерлейкина (IL)-2 в иммунопатогенезе ревматоидного артрита (РА), оценить опыт применения клинический низких доз IL-2 (ldIL-2) для терапии РА и определить перспективы Treg-селективных препаратов данного цитокина, включая таргетную доставку IL-2 в регуляторные T-клетки. Материал и методы. Выполнен целевой поиск в базах данных PubMed ClinicalTrials.gov и ChiCTR от момента их индексирования до 2026 г. Запросы включали следующие ключевые термины: rheumatoid arthritis, interleukin-2, low-dose IL-2, regulatory T cells, FOXP3, STAT5, CD25, IL2RA, IL-2 mutein, targeted delivery, TNFR2, CTLA-4, GARP/LRRC32, GITR, OX40, ICOS, CD39, CD73, CCR4, CCR8, CXCR5. Основные положения. IL-2 способствует выживанию и функциональной стабильности Treg, стимулируя экспрессию FOXP3. При РА нарушения иммунорегуляции могут проявляться уменьшением численности Treg, снижением их супрессорной активности или недостаточной функциональностью в условиях воспаленной микросреды синовии. Применение низких доз IL-2 в пилотных исследованиях показало увеличение количества циркулирующих Treg, однако сегодня имеющихся данных недостаточно для оценки устойчивого клинического эффекта и оптимального режима терапии. Перспективными направлениями разработок представляются инженерные варианты IL-2 с повышенной селективностью в отношении Treg, включая мутеины IL-2, пегилированные и слитые с Fc-доменом формы, бифункциональные белки с IL-2 и агентами для адресной доставки нацеленные на преимущественно экспрессируемые Treg поверхностные мишени. Заключение. Сегодня применение IL-2 не является стандартом терапии РА, но представляет перспективную стратегию для восстановления толерантности. Наиболее важные ближайшие задачи: доказать клиническую эффективность, определить эндотипы пациентов для повышения эффективности лечения и повысить Treg-селективность доставки IL-2.
Ключевые слова
Авторы и аффилиации
https://elibrary.ru/fwnqef А.О. Соловьева(1), М.Л. Филипенко(2), М.А. Королев(1)
1-Научно-исследовательский институт клинической и экспериментальной лимфологии –
филиал Федерального государственного бюджетного научного учреждения
«Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения
Российской академии наук», Российская Федерация, 630117, Новосибирск, ул. Арбузова д. 6;
2-Институт химической биологии и фундаментальной медицины им. Д.Г. Кнорре,
Российская Федерация, 630090, Новосибирск, пр. Ак. Лаврентьева, 8
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