A model depicting the roles of TLR3 in liver injury, inflammation, regeneration, and fibrosis. Poly I:C or dsRNA binds TLR3 receptor in NK cells and stimulates NK cells to produce IFN- that induces hepatocyte cell cycle arrest and apoptosis via activation of STAT1. IFN- also induces stellate cell cycle arrest and apoptosis in an STAT1-depdent manner, resulting in inhibition of liver fibrosis. Poly I:C can also inhibit liver fibrosis via activation of NK cell killing of early activated stellate cells. In addition, poly I:C or dsRNA targets TLR3 in many other cell types, followed by production of IFNs, chemokines, and anti-inflammatory cytokines, resulting in liver inflammation.
