Activated hepatic stellate cells and natural killer cells (aHSC-NK cell axis)

Activated hepatic stellate cells (aHSCs) and natural killer (NK) cells represent a critical cellular axis in the regulation of liver fibrosis and tissue repair. aHSCs are the primary drivers of fibrogenesis, transforming from quiescent vitamin A-storing cells into proliferative, contractile myofibroblasts that secrete excessive extracellular matrix in response to chronic injury (PMID: 22438534). NK cells act as an innate immune checkpoint by selectively identifying and eliminating these aHSCs, thereby promoting the resolution of fibrosis (PMID: 16456602). This clearance is mediated by the interaction between NK cell activating receptors, such as NKG2D, and stress-induced ligands on aHSCs, alongside the induction of apoptosis via the TRAIL pathway. Therapeutic strategies targeting this interaction aim to enhance NK cell cytotoxicity or utilize engineered CAR-NK cells to specifically target aHSC markers, offering a potential treatment for chronic liver diseases like cirrhosis and non-alcoholic steatohepatitis (NASH) (PMID: 31948744).

Other names

NK-HSC interactionHepatic stellate cell-Natural killer cell axisaHSC-NK cell interplayImmune-mediated HSC clearance

Natural killer (NK) cells limit liver fibrosis by inducing apoptosis in activated hepatic stellate cells (aHSCs) through the engagement of NKG2D receptors and TRAIL-mediated signaling, as well as through the production of antifibrotic cytokines like interferon-gamma (PMID: 16456602).