Natural Killer T Cells in Various Mouse Models of Hepatitis

Figure 3

Alcohol stimulates KC to secrete IL-1β, which mediates the accumulation and activation of liver iNKT cells. iNKT cells promote neutrophil infiltration and liver inflammation by upregulating the expression of OPN, IL-4, IL-6, MIP-1α, MIP-2, and TNF-α. Activated iNKT cells also secrete IL-10 to inhibit the number and function of NK cells. In vitro, NK cells and secreted IFN-γ can protect the liver from steatosis. Chronic ethanol consumption stimulates HSCs to secrete TGF-β1 to downregulate NKG2D and TRAIL expression on NK cells, leading to an impaired ability to kill HSCs and antagonizing the IFN-γ antifibrosis effect. Figure created with BioRender (https://biorender.com). Abbreviations: (+): activate; (-): inhibit; NK: natural killer cell; NKT: natural killer T cell; IL: interleukin; OPN: osteopontin; IFN-γ: interferon-gamma; MIP: macrophage inflammatory protein; TNF-α: tumor necrosis factor-α; TGF-β1: transforming growth factor-β1; HSC: hepatic stellate cell; KC: Kupffer cell; TRAIL: TNF-related apoptosis-inducing ligand; HSC: hepatic stellate cells.