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dc.creatorPerugorria, M.J. (María J.)-
dc.creatorEsparza-Baquer, A. (Aitor)-
dc.creatorOakley, F. (Fiona)-
dc.creatorLabiano, I. (Ibone)-
dc.creatorKorosec, A. (Ana)-
dc.creatorJais, A. (Alexander)-
dc.creatorMann, J. (Jelena)-
dc.creatorTiniakos, D. (Dina)-
dc.creatorSantos-Laso, A. (Alvaro)-
dc.creatorArbelaiz, A. (Ander)-
dc.creatorGawish, R. (Riem)-
dc.creatorSampedro, A. (Ana)-
dc.creatorFontanellas, A. (Antonio)-
dc.creatorHijona, E. (Elizabeth)-
dc.creatorJimenez-Agüero, R. (Raul)-
dc.creatorEsterbauer, H. (Harald)-
dc.creatorStoiber, D. (Dagmar)-
dc.creatorBujanda, L. (Luis)-
dc.creatorBanales, J.M. (Jesús M.)-
dc.creatorKnapp, S. (Sylvia)-
dc.creatorSharif, O. (Omar)-
dc.creatorMann, D.A. (Derek A.)-
dc.identifier.citationPerugorria, M.J. (María J.); Esparza-Baquer, A. (Aitor); Oakley, F. (Fiona); et al. "Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage". Gut. 68 (3), 2019, 533 - 546es
dc.description.abstractObjective: 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. Design: 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 Trem-2-/- mice. Primary liver cells from both genotypes of mice were isolated for in vitro experiments. Results: 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 Trem-2-/- 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. Conclusion: 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.es_ES
dc.description.sponsorshipThe present study was supported by grants from the Wellcome Trust (grant WT086755MA), European Commission FP7 program grant ’INFLA-CARE’ (EC Contract No. 223151;), the Medical Research Council, UK (grant MR/K001949/1) and Cancer Research UK Programme Grant C18342/A2390. to DAM. The study was also funded by the Basque Government’s Department of Industry, Innovation, Commerce and Tourism, SAIOTEK Programme grant (SAIO13-PE13BN010) and the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III grant (PI14/00399), both to MJP. MJP was funded by IKERBASQUE, Basque foundation for Science and the Ministry of Economy and Competitiveness, Ramón y Cajal Programme (RYC-2015-17755). AE-B was funded by the University of the Basque Country (UPV/EHU; PIF2014/11). IL was funded by the Department of Education, Language Policy and Culture of the Basque Government (PRE_2016_1_0152). RG was funded by the Austrian Science Fund (FWF; APW01205FW, within the Doctoral Program Cell Communication in Health and Disease, CCHD; to SK). OS and SK were funded by the Austrian Science Fund (OS, FWF-25801; SK, Grant I 289-B09).es_ES
dc.relationinfo:eu-repo/grantAgreement/WT/Physiology in Health and Disease/086755-
dc.relationinfo:eu-repo/grantAgreement/UKRI/MRC/MR%2FK001949%2F1 /GB/MICA: Illuminating mechanisms regulating the birth, life and death of the myofibroblast to inform the development of antifibrotics for liver disease. /MICA-
dc.relationinfo:eu-repo/grantAgreement/FWF/Internationale Projekte/I 289/AT/Innate immune responses to Streptococcus pyogenes//-
dc.subjectAcute liver failurees_ES
dc.subjectChronic liver diseasees_ES
dc.subjectHepatic stellate celles_ES
dc.subjectImmune-mediated liver damagees_ES
dc.titleNon-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damagees_ES
dc.description.noteThis is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/ licenses/by/4.0/.es_ES

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