Figure 1

A proposed model depicting the opposing roles of type I and type II NKT cells in inflammatory diseases in the liver. Type I NKT cells are rapidly activated following liver injuries induced by alcohol, high-fat diet, ischemia and/or gut-derived microbial products. Liver-resident antigen-presenting cells, such as KCs, and TLRs/cytokines mediate their activation, which results in the cytokine/chemokine-dependent recruitment of myeloid cells (CD11b+Gr-1+) and neutrophils, and the activation of HSC and NK cells. These cellular interactions lead to steatosis, fibrosis and hepatocyte necrosis. These events are also involved in the development of HCC. In contrast, type II NKT cells are activated following the presentation of self-lipids, such as sulfatide and LPC, which results in the induction of a cross-regulatory pathway that inhibits type I NKT cells, tolerizes cDCs and blocks the inflammatory cascade and liver disease. cDCs, conventional DCs; HCC, hepatocellular carcinoma; HSC, hepatic stellate cell; KC, Kupffer cell; LPC, lysophosphatidylcholine; NK, natural killer; NKT, natural killer T cells; OPN, osteopontin; TLR, toll-like receptor.