Natural killer cell dysfunction drives keloid pathogenesis - PubMed
5 hours ago
- #immunoregulation
- #NK cells
- #keloid pathogenesis
- Keloids are pathological scars caused by dysregulated wound healing, featuring fibroblast hyperproliferation and excessive extracellular matrix deposition.
- Natural killer (NK) cells play a dual role: they limit aberrant cell growth via IFN-γ but also produce amphiregulin (AREG), which promotes tissue repair and cell survival.
- In keloid lesions, NK cell-derived IFN-γ restricts fibroblast survival and matrix production, while AREG counteracts these effects.
- Fibroblast-derived TGF-β suppresses NK cell IFN-γ production, creating a local immunoregulatory loop.
- Systemically, keloid patients show elevated plasma IFN-β, leading to a distinct circulating NK cell subset with reduced IFN-γ production and increased IFN-stimulated genes.
- Elevated IFN-β suppresses PI3K-AKT signaling, promoting NK cell exhaustion through mitochondrial and metabolic dysfunction, linking local and systemic NK cell dysregulation in keloids.