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

Figure 1 Structure and function of triggering receptor expressed on myeloid cells 2. A: Triggering receptor expressed on myeloid cells (TREM) 2 consists of a signal peptide, an extracellular domain containing a V-type immunoglobulin domain, a short stalk sequence, a transmembrane helix, and a cytoplasmic tail; B: After binding to TREM2, ligands such as high-density lipoprotein, low-density lipoproteins, lipopolysaccharide, apolipoprotein, and other ligands bind to adaptor proteins DNAX-activating proteins (DAP) 12 and DAP10 to form a ligand-receptor complex, which triggers the phosphorylation of the immune receptor tyrosine-based activation motif in the cytoplasmic region of DAP12, recruiting and mediating spleen tyrosine kinase (Syk) phosphorylation, thereby activating downstream signaling pathways such as phosphatidylinositol 3-kinase, mitogen-activated protein kinase, extracellular regulating kinase, and c-Jun N-terminal kinase signaling pathways; C: During the early formation of the TREM2-DAP12 complex, the recruitment of Syk to DAP12 and the activation of downstream signaling can be blocked by Src homology 2-containing inositol-5'-phosphatase 1; D: TREM2 can also be cleaved by a disintegrin and metalloproteinase (ADAM) 10, ADAM17, and γ-secretase to release soluble TREM2. ADAM: A disintegrin and metalloproteinase; APOE: Apolipoprotein E; DAP: DNAX-activating proteins; ERK: Extracellular regulating kinase; HDL: High-density lipoprotein; ITAM: Immune receptor tyrosine-based activation motif; JNK: C-Jun N-terminal kinase; LDL: Low-density lipoproteins; LPS: Lipopolysaccharide; MAPK: Mitogen-activated protein kinase; PI3K: Phosphatidylinositol 3-kinase; STREM2: Soluble triggering receptor expressed on myeloid cells 2; Syk: Spleen tyrosine kinase; TREM2: Triggering receptor expressed on myeloid cells 2.