Эпигенетическая модуляция иммунной толерантности при болезни Грейвса: роль короткоцепочечных жирных кислот в регуляции синтеза АТ-рТТГ

Болезнь Грейвса представляет собой системный аутоиммунный процесс, в основе которого лежит стойкое нарушение иммунной толерантности и персистенция антител к рецептору тиреотропного гормона (АТ-рТТГ), сохраняющаяся даже после радикального удаления щитовидной железы (ЩЖ). В представленном обзоре рассматривается роль оси «кишечник — щитовидная железа» в качестве ключевого регулятора системного иммунного гомеостаза. Особое внимание уделено короткоцепочечным жирным кислотам (КЦЖК) — продуктам микробного метаболизма, которые выступают в качестве мощных эпигенетических модуляторов. Детально описаны механизмы ингибирования гистондеацетилаз (HDAC) бутиратом и пропионатом, что способствует стабилизации экспрессии гена Foxp3 в регуляторных Т-клетках и подавлению факторов дифференцировки В-лимфоцитов (AID, Blimp-1). Проанализирована взаимосвязь между кишечным дисбиозом, повышенной проницаемостью барьера и неконтролируемой продукцией аутоантител. В заключении обсуждаются перспективные стратегии таргетной терапии, включая трансплантацию фекальной микробиоты (ТФМ) и использование селективных ингибиторов HDAC, направленных на восстановление иммунного контроля при рефрактерных формах заболевания.

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