DNA-PK-mediated phosphorylation of STAT6 establishes a non-canonical type 2 immunity axis to prevent macrophage senescence - PubMed
6 hours ago
- #DNA repair
- #macrophage senescence
- #inflammaging
- DNA-PK-mediated phosphorylation of STAT6 at serine 807 (Ser807) prevents macrophage senescence.
- Phosphorylation of STAT6 blocks its degradation and promotes DNA repair gene activation via PU.1 partnership.
- Lack of Ser807 phosphorylation leads to DNA repair defects, macrophage senescence, and inflammaging.
- In vivo, STAT6(S807A) mutant accelerates macrophage senescence, tissue fibrosis, and systemic aging.
- Transfer of phosphomimetic STAT6(S807E)-expressing macrophages rescues accelerated aging.
- Reduced phosphorylation of human STAT6 (Ser817) in COPD patients correlates with increased DNA damage and senescence.
- The DNA-PK-STAT6 axis represents a non-canonical type 2 immunity mechanism via DNA repair for healthy aging.