Стерильное воспаление, кросспрезентация, аутофагия и адаптивный иммунитет при иммуновоспалительных ревматических заболеваниях

Доминирующими этиологическими факторами стерильного воспаления при иммуновоспалительных ревматических заболеваниях являются провоспалительные вне- и внутриклеточные DAMPs, генерирующиеся при системной прогрессирующей дезорганизации рыхлой волокнистой неоформленной соединительной ткани, регулируемой гибели клеток и некрозе клеток. Стерильное воспаление является многоступенчатым процессом, при котором индуцируется последовательность реакций, опосредованных лейкоцитами и резидентными клетками макрофагально-моноцитарного ряда, направленных на очищение очага воспаления от клеточного и тканевого детрита, с последующим восстановлением гомеостаза поврежденной ткани. Важная роль в этом процессе принадлежит трансэндотелиальной миграции лейкоцитов в очаг стерильного воспаления и формирование клеточного воспалительного инфильтрата. Ключевой особенностью указанных процессов является реактивность PRR-рецепторов и, как следствие PRR-DAMPs взаимодействий, последующий запуск молекулярноклеточных процессов, итогом которых является картина локальных и/или системных проявлений стерильного воспаления. Следствием PRR-DAMPs взаимодействий является активация врожденного иммунитета и запуск молекулярно-клеточных реакций, позволяющих отнести иммуновоспалительные ревматические заболевания к категории системных стерильных аутовоспалительных процессов. Генерализованность патофизиологических эффектов провоспалительных DAMPs и, соответственно, системность и полиорганность поражения тканей и внутренних органов при иммуновоспалительных ревматических заболеваниях обусловлено широкой распространенностью рецепторов к «сигналам опасности». В развитии DAMP-опосредованного стерильного воспаления важнейшее место занимает феномен кросс-презентации и аутофагия. Кросс-презентация обуславливает презентацию внеклеточных DAMPs из интернализованных белков с молекулами МНС класса I аутореактивным CD8⁺ цитотоксическим Т-лимфоцитам. Аутофагия обеспечивает процессинг внутриклеточных пептидных DAMPs, их загрузку на молекулы МНС класса II с последующей индукцией CD4⁺Т-клеточного адаптивного иммунного ответа. Важный вклад в указанные процессы вносят врожденные лимфоидные клетки. Модель функциональной сопряженности и взаимодополняемости ILCs и Th-CD4⁺Т-клеток расширило наши представления об иммунной регуляции, распространив активность врожденного и адаптивного иммунитета в область поддержания тканевого гомеостаза, морфогенеза, репарации, регенерации и воспаления. Следствием PRR-DAMP взаимодействий тканевых ILCs и последующего подключения клеточных пар ILC – Th-CD4⁺Т-клеток является прогрессирование системного стерильного воспаления. Представленные в настоящем обзоре материалы определяют перспективные молекулярные и клеточные мишени с целью регуляции и/или ингибирования активности стерильного воспаления при иммуновоспалительных ревматических заболеваниях.

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