Role of triggering receptor expressed on myeloid cells 2 in the pathogenesis of non-alcoholic fatty liver disease

Figure 3 Regulatory role of triggering receptor expressed on myeloid cells 2 in non-alcoholic fatty liver disease-related inflammatory injury. The liver macrophages expressing Triggering receptor expressed on myeloid cells 2 (TREM2) exhibit inhibition of the pro-inflammatory response caused by toll like receptor (TLR) 4-driven extracellular regulating kinase and mitogen-activated protein kinase phosphorylation activation, as well as reactive oxygen species-mediated lipid peroxidation and hepatocyte death. High expression of TREM2 ensures that macrophages can effectively clear apoptotic hepatocytes through efferocytosis in a timely manner, thereby inhibiting the transformation of non-alcoholic fatty liver disease into non-alcoholic steatohepatitis (NASH). TREM2 can induce macrophage differentiation towards M2 macrophages and inhibit inflammatory response. Tumor necrosis factor and interleukin-1β can induce a disintegrin and metalloproteinase 17 to cleave TREM2, leading to an increase in soluble TREM2 levels and aggravation of inflammation in NASH. TREM2 can also inhibit the production of TLR4-dependent monocyte chemoattractant protein-1 in hepatic stellate cells. The TREM2 receptor expressed in dendritic cells inhibits nuclear factor-kappa B through binding with DNAX-activating proteins 12, thereby alleviating liver inflammation. ADAM: A disintegrin and metalloproteinase; DAP: DNAX-activating proteins; STREM2: Soluble triggering receptor expressed on myeloid cells 2; TREM: Triggering receptor expressed on myeloid cells 2.