Function of TREM1 and TREM2 in Liver-Related Diseases

Abstract

TREM1 and TREM2 are members of the triggering receptors expressed on myeloid cells (TREM) family. Both TREM1 and TREM2 are immunoglobulin superfamily receptors. Their main function is to identify foreign antigens and toxic substances, thereby adjusting the inflammatory response. In the liver, TREM1 and TREM2 are expressed on non-parenchymal cells, such as liver sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells, and cells which infiltrate the liver in response to injury including monocyte-derived macrophages and neutrophils. The function of TREM1 and TREM2 in inflammatory response depends on Toll-like receptor 4. TREM1 mainly augments inflammation during acute inflammation, while TREM2 mainly inhibits chronic inflammation to protect the liver from pathological changes. Chronic inflammation often induces metabolic abnormalities, fibrosis, and tumorigenesis. The above physiological changes lead to liver-related diseases, such as liver injury, nonalcoholic steatohepatitis, hepatic fibrosis, and hepatocellular carcinoma. Here, we review the function of TREM1 and TREM2 in different liver diseases based on inflammation, providing a more comprehensive perspective for the treatment of liver-related diseases.

SYK-3BP2 Pathway Activity in Parenchymal and Myeloid Cells Is a Key Pathogenic Factor in Metabolic Steatohepatitis

“… 41 An important additional amplifier of TLR4-mediated hepatic inflammation is the TREM1/DAP12 pathway. 23 , 24 , 25 Interestingly, we here report that the prevention of liver inflammation and injury mediated by the targeting of 3BP2 or SYK strongly decrease TREM1/DAP12 expression. Because of the central place of the SYK pathway in both TLR4 and TREM-1 signaling, 23 this suggests the establishment of an inflammatory loop in which SYK and its partner 3BP2 exacerbate liver inflammation.…”

“…This effect of the hepatic inflammation was also confirmed by the decreased hepatic expression of CD44 and SYK at the protein level (Figure 3H) and decreased serum level of CCL2 (Figure 3I). In addition, the hepatic expression of Trem1, an important amplifier of TLR4 pathway via SYK activity, 15,[23][24][25] decreased in MCDD-fed Sh3bp2 -/mice compared with MCDD-fed Wt mice (Figure 3G). In line with this, the expression of Dap12, the transmembrane adaptor required for TREM1 function, also decreased (Figure 3G).…”

“…In addition, TREM1, a member of the triggering receptors expressed on myeloid cells (TREM) family that mediates the inflammatory response through TLR4, DNAX-activation protein of 12 kDa (DAP12), and SYK, has been implicated in liver diseases. [23][24][25] In line with the important role of the SYK pathway in inflammatory diseases, gain-of-function mutations in SYK, leading to increased phosphorylation and hyperactivated downstream signaling, were recently associated with immune dysfunction and systemic inflammation. 26 Among the components of the SYK pathway, 13 we have previously shown that 3BP2 (also known as SH3 binding protein 2), a cytoplasmic adapter that interacts with SYK, [27][28][29][30] was necessary for TLR-mediated activation of macrophages in response to PAMPs and DAMPs.…”

Plasma Nesfatin-1: Potential Predictor and Diagnostic Biomarker for Cognitive Dysfunction in T2DM Patient

“…As members of the triggering receptors expressed on myeloid cells (TREM) family, TREM1 and TREM2 participate in the regulation of inflammation and immune response by modulating the secretion of inflammatory cytokines such as TNF-α, IL-1β, and IL-6. 30 Recent studies have indicated that the missense mutation and expression changes of TREM1 and TREM2 are closely related to cognitive dysfunction in patients with AD. 31 , 32 Clinical studies have shown that the level of TREM2 in the peripheral blood of patients with AD increased significantly.…”

Proteína de transferência de colesterol esterificado (CETP) altera a polarização de macrófagos M1 e M2 agravando o enfisema pulmonar experimental induzido por elastase

“…Os macrófagos, em geral, expressam outras moléculas importantes e determinantes na sua polarização em M1 ou M2 como TREM1 (Triggering Receptor Expressed on Myeloid Cells-1), o TIM3 (T cell immunoglobulin and mucin domain-3) e a galectina 9. O TREM1 é um receptor da família das imunoglobulinas, com função principal de identificar antígenos, modulando a resposta inflamatória (Sun et al, 2020).…”