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In humans, two genes on chromosome 6p21 encode the triggering receptors expressed on myeloid cells-1 (TREM1) and triggering receptor expressed on myeloid cells-2 (TREM2), members of the immunoglobulin-lectin-like superfamily.1 Interestingly, the activation of TREM1 and TREM2 results in divergent cellular responses. While TREM1 promotes inflammation, TREM2 exerts anti-inflammatory effects, thus maintaining tissue homeostasis during pathological processes.
The possibility of modulating TREM2 recently caught the eye of researchers and industry for the exploration of its cell-specific biological role in inflammation-derived disorders for future pharmacological development. TREM2 is expressed in immature monocyte-derived dendritic cells (DCs), certain neutrophils and tissue-specific macrophages, including osteoclasts and microglia.2 Indeed, the impact of TREM2 as a sensor of inflammation during tissue injury was analysed and reported in neurogenerative disorders,3 obesity,4 atherosclerosis,5 fatty liver disease2 and tumorigenesis (eg, glioma and gastric cancer).2
Evidence for the function of TREM2 in the liver has been recollected not only from human tissue but also from a wide array of preclinical models of liver injury ranging from acute (toxic) liver injury to advanced chronic liver disease and end-stage hepatocellular carcinoma (HCC).
During acute liver injury, TREM2 functions to dampen hepatic damage via the modulation of the inflammatory response. TREM2-deficient Kupffer cells (KCs) when exposed to lipopolysaccharide displayed induction of inflammatory cytokines (eg, interleukin-6 and tumour necrosis factor). Moreover, experimental toxic liver injury—carbon tetrachloride or acetaminophen overdose—further corroborated the critical role of TREM2 in maintaining liver function by suppressing the monocyte chemoattractant protein-1 (MCP-1)-derived …
Contributors FJC drafted and wrote the commentary.
Funding The MINECO Retos SAF2016-78711, EXOHEP-CM S2017/BMD-3727, NanoLiver-CM Y2018/NMT-4949, ERAB Ref. EA 18/14, AMMF 2018/117, COST Action CA17112 and UCM-25/2019. FJC is a Ramón y Cajal Researchers RYC-2014–15242 and a Gilead Liver Research Scholar 2018. The research group belongs to the validated Research Groups Ref. 970935 “Liver Pathophysiology” and 920631 'Lymphocyte immunobiology' and IBL-6 (imas12-associated).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Provenance and peer review Commissioned; internally peer reviewed.
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