Аутофагия, апоптоз, некроптоз, пироптоз и нетоз в патогенезе иммуновоспалительных ревматических заболеваний

При иммуновоспалительных ревматических заболеваниях организованными формами клеточного инфильтрата являются эктопические фолликулоподобные лимфоидные структуры и ГЗТ-гранулемы, неорганизованными формами — диффузный клеточный воспалительный инфильтрат. Неотъемлемым компонентом патогенетической динамики этих видов клеточного инфильтрата являются программируемые варианты гибели клеток, из которых наиболее значимыми являются аутофагия, апоптоз, некроптоз, пироптоз и нетоз. Существует тесная взаимосвязь между указанными формами клеточной гибели. Эта взаимосвязь сформировалась в процессе биологической эволюции, отличается выраженным консерватизмом и подчиняется общебиологическим закономерностям молекулярно-клеточных процессов в клетке. Высвобождающиеся в процессе гибели клеток «сигналы опасности» (DAMPs) индуцируют состояние аутореактивности, обусловленной в том числе модуляцией процессов гибели клеток с помощью PRR-рецепторов клеток врожденной иммунной системы. На основании анализа процесса эндоцитоза, сигнальных путей, адапторных молекул, транскрипционных факторов, свойственных каждой из указанных форм гибели клеток, представлена патогенетическая значимость изменений мембранных структур и молекулярных путей реализации программируемой клеточной гибели при иммуновоспалительных ревматических заболеваниях. В этом отношении фундаментальными являются мембран-ассоциированные клеточные процессы, формирование различных видов внутриклеточных инфламмасом, процессы кросс-презентации МНС-рестриктированных продуктов дезорганизации рыхлой волокнистой соединительной ткани и индукция аутореактивности врожденной и адаптивной иммунных систем. Причинно-следственные взаимоотношения молекулярных путей реализации указанных форм клеточной гибели позволяют идентифицировать целевые молекулярные мишени с целью модуляции продуктивного воспаления.

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