Возрастная инволюция тимуса: механизмы ремоделирования T-клеточного иммунитета

обзоре систематизированы современные представления о молекулярных, клеточных и нейроэндокринных механизмах возрастной инволюции тимуса и её роли в формировании иммуностарения (immunosenescence) и онкопатологии. Проанализированы ключевые транскрипционные факторы (Foxn1, E2F3, Myc), сигнальные каскады (Notch/DLL4, PPARγ) и эпигенетические регуляторы (miR-181a), координирующие деградацию тимусных эпителиальных клеток и замещение паренхимы жировой тканью. Особое внимание уделено роли половых стероидов в индукции атрофии органа, физиологическим особенностям гестационной инволюции (ось RANK/прогестерон), а также протективным эффектам калорической рестрикции и соматотропной оси (GH/ IGF-1). С клинической точки зрения охарактеризовано влияние деградации медуллярного компартмента на искажение негативной селекции и накопление супрессорных пулов Т-регуляторных клеток (tTreg), блокирующих противоопухолевый надзор в пожилом возрасте. Обоснована перспективность использования кольцевых ДНК-эксцизий Т-клеточного рецептора (TREC) в качестве прецизионного биомаркера истинного функционального сенесценса тимуса.

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