Figure 1.

NK cell interactions with liver cells during NAFLD/NASH progression. At early stages of NAFLD, NK cells promote TRAIL-mediated death of hepatic stellate cells (HSC). NK cells promote the activation of other immune cells in the liver including macrophages via IFN-γ. Lipid accumulation in hepatocytes contributes to the expression of stress ligands that may promote the upregulation of the activating receptor NKG2D. This is relevant at later stages of NASH where increased activation of NKG2D by ligands including MICA (in patients) promote activation of NK cells. Loss of cytotoxic and tumoricidal activity in NK cells may contribute to the progression of hepatocellular carcinoma (HCC) at later stages of the disease. Figure created with BioRender.com.