TLR3 Mediates Senescence and Immunosurveillance of Hepatic Stellate Cells

BackgroundActivation of hepatic stellate cells (HSCs) is an important driver of liver fibrosis, which is a health problem of global concern, and there is no effective solution for it at the present. Senescent activated HSCs are preferentially killed by natural killer cells (NK cells) to promote the regression of hepatic fibrosis.ObjectivesThe purpose of this study was to investigate the effect of polyinosinic-polycytidylic acid (poly I:C) on HSCs’ senescence, a trigger for NK cell-induced cytotoxicity.MethodsThe senescence of HSCs was assessed by western blot, qRT-PCR, and flow cytometry, and NK cell cytotoxicity was assessed in a co-culture of NK cells with poly I:C-treated HSCs by measuring CD107a expression.ResultsThe expression of p16, p21, SA--gal, MICA/MICB, and ULBP2 increased in poly I:C-treated HSCs, rendering them significantly susceptible to NK cell cytotoxicity.ConclusionsPoly I:C induces cellular senescence in HSCs and triggersNKcellimmunosurveillance, suggesting that the role of poly I:C in HSC senescence may promote fibrosis regression.