Details

Autor(en) / Beteiligte

• Perugorria, Maria J
• Esparza-Baquer, Aitor
• Oakley, Fiona
• Labiano, Ibone
• Korosec, Ana
• Jais, Alexander
• Mann, Jelena
• Tiniakos, Dina
• Santos-Laso, Alvaro
• Arbelaiz, Ander
• Gawish, Riem
• Sampedro, Ana
• Fontanellas, Antonio
• Hijona, Elizabeth
• Jimenez-Agüero, Raul
• Esterbauer, Harald
• Stoiber, Dagmar
• Bujanda, Luis
• Banales, Jesus María
• Knapp, Sylvia
• Sharif, Omar
• Mann, Derek A

Titel

Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage

Ist Teil von

• Gut, 2019-03, Vol.68 (3), p.533-546

Ort / Verlag

England

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Liver injury impacts hepatic inflammation in part via Toll-like receptor (TLR) signalling. Triggering receptor expressed on myeloid cells 2 (TREM-2) modulates TLR4-mediated inflammation in bone marrow (BM)-derived macrophages but its function in liver injury is unknown. Here we hypothesised that the anti-inflammatory effects of TREM-2 on TLR signalling may limit hepatic injury. TREM-2 expression was analysed in livers of humans with various forms of liver injury compared with control individuals. Acute and chronic liver injury models were performed in wild type and mice. Primary liver cells from both genotypes of mice were isolated for in vitro experiments. TREM-2 was expressed on non-parenchymal hepatic cells and induced during liver injury in mice and man. Mice lacking TREM-2 exhibited heightened liver damage and inflammation during acute and repetitive carbon tetrachloride and acetaminophen (APAP) intoxication, the latter of which TREM-2 deficiency was remarkably associated with worsened survival. Liver damage in mice following chronic injury and APAP challenge was associated with elevated hepatic lipid peroxidation and macrophage content. BM transplantation experiments and cellular reactive oxygen species assays revealed effects of TREM-2 in the context of chronic injury depended on both immune and resident TREM-2 expression. Consistent with effects of TREM-2 on inflammation-associated injury, primary hepatic macrophages and hepatic stellate cells lacking TREM-2 exhibited augmented TLR4-driven proinflammatory responses. Our data indicate that by acting as a natural brake on inflammation during hepatocellular injury, TREM-2 is a critical regulator of diverse types of hepatotoxic injury.