Figure 5 Model of the crosstalk between Kupffer cells and NK cells in PBC mice. 1) RAE-l expressed on Kupffer cells directly activates NK cells by its interaction with NKG2D. 2) Kupffer cell-derived IL-12 and TNF-α help to indirectly stimulate the production of IFN-γ by NK cells. 3) NK cell-derived IFN-γ stimulates the increased production of IL-12 and TNF-α by Kupffer cells. 4) Kupffer cell-derived IL-12 and TNF-α and NK cell-derived IFN-γ synergistically induce biliary epithelial cell damage. NK – natural killer; PBC – primary biliary cholangitis; RAE-1 – retinoic acid early inducible-1 – NKG2D, natural killer group 2, member D; IL – interleukin; TNF – tumor necrosis factor; IFN-γ – interferon-γ.