Аутоиммунный увеит: факторы риска и проблемы иммунопатогенеза

Представлены последние достижения в понимании механизмов, лежащих в основе предрасположенности к иммуноопосредованному увеиту (ИУ) и его патогенеза. Подробно описаны модели увеита человека на животных, среди которых наиболее охарактеризованными моделями экспериментального переднего увеита являются эндотоксин-индуцированный увеит и экспериментальный аутоиммунный передний увеит. В результате этих исследований были идентифицированы такие факторы транскрипции как STAT3, Interferon regulatory factor 4,8, регуляторные белки - Suppressor of cytokine signaling 1, 3 (SOCS1 , SOCS3 ) и пути передачи сигналов цитокинов, которые регулируют развитие ИУ и могут служить потенциальными терапевтическими мишенями для лечения. Охарактеризованы факторы риска окружающей среды способствующие развитию ИУ. Представлены данные о влиянии физической активности, курения, состояния микробиома кишечника, диеты на частоту возникновения ИУ, описаны известные и предполагаемые механизмы участия факторов риска в инициации и патогенезе болезни. В частности, изложены результаты исследований свидетельствующих о существовании двух основных механизмов участия микробиома кишечника в развитии ИУ: антигены микробиома кишечника действуют как триггеры активации Т-клеток, специфичных для антигенов сетчатки и микробиом модулирует баланс эффекторных субпопуляций Т – лимфоцитов (Th1 и Th17) и субпопуляций иммунорегуляторных клеток (Treg). Изложены сведения о том, что высокий уровень экспрессии глазных белков (межфоторецепторный ретиноид-связывающий белок - IRBP или S-антиген) в тимусе коррелировал с устойчивостью к развитию EAU, тогда как низкий уровень коррелировал с предрасположенностью к увеиту. Эти основополагающие исследования патогенеза ИУ позволило дать объяснение избирательной восприимчивости к аутоиммунному увеиту и предположить, что резистентность к увеиту регулируется, по крайней мере частично, способностью сохранять центральную толерантность к аутоантигенам сетчатки. Описано, что увеитогенные Т-клетки памяти перемещаются из сетчатки и периферических лимфоидных тканей в костный мозг, находясь там в состоянии покоя до повторной стимуляции, превращаясь в различные субпопуляции эффекторных клеток. Анализ результатов иммунологических исследований на модели увеита у мыши и перферической крови пациентов с увеитом человека выявил патогенетическую роль Th17-лимфоцитов и активатора транскрипции STAT3 в развитии аутоиммунного увеита и сигнальный белок STAT3 является потенциальной терапевтической мишенью при неинфекционном увеите.

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