Fig. 3

Immune cell function in liver pathologies. A Liver cancer risk factors include alcohol-induced liver injury, which is associated with an increase in endotoxins in the liver that activate Kupffer cells to produce TNF-α and IL-6. This results in increased production of complement factors that drive an inflammatory environment. In pathogen infection, group 1 ILCs and cytotoxic T cells can recognize and eliminate infected hepatocytes. ILC1s can express PD-L1 in settings of chronic infection, which negatively regulates adaptive immune responses. Kupffer cells can be both proinflammatory and anti-inflammatory. Proinflammatory Kupffer cells produce TNF-α, and anti-inflammatory Kupffer cells produce TGF-β. Monocytes can regulate T cells to produce the proinflammatory cytokine IL-17. Obesity activates a cascade in which Kupffer cells produce TNF-α and IL-6, resulting in chronic inflammation and the development of fatty liver disease. B Chronic inflammation can lead to liver fibrosis. NK cells and ILC1s can directly recognize and eliminate activated stellate cells in the fibrotic liver, a pathway that can be inhibited by TGF-β secretion. C Sustained inflammation and fibrosis can result in the development of hepatocellular carcinoma. NK cells can directly kill cancerous cells but ultimately can become dysfunctional, for example, in response to TGF-β, which is highly expressed in hepatic inflammation. These dysfunctional NK cells express receptors that negatively regulate their cytotoxicity. CD49a⁺ ILC1s can inhibit NK cell function and promote cancer growth by producing proangiogenic factors allowing tumor growth