{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:14:33Z","timestamp":1788434073192,"version":"build-2803163510"},"reference-count":37,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","journal-of-hepatology.eu","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Hepatology"],"published-print":{"date-parts":[[2022,10]]},"DOI":"10.1016\/j.jhep.2022.05.044","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T21:56:43Z","timestamp":1655848603000},"page":"991-1004","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":79,"title":["TREM-2 plays a protective role in cholestasis by acting as a negative regulator of inflammation"],"prefix":"10.1016","volume":"77","author":[{"given":"Ibone","family":"Labiano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alo\u00f1a","family":"Agirre-Lizaso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Olaizola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Echebarria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maider","family":"Huici-Izagirre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Olaizola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aitor","family":"Esparza-Baquer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Sharif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Hijona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Milkiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Milkiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Gonz\u00e1lez-Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Aspichueta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Monte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose J.G.","family":"Marin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihael","family":"Vucur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Luedde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Marzioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek A.","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Bujanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro M.","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus M.","family":"Banales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Perugorria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jhep.2022.05.044_bib1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3727\/105221619X15614873062730","article-title":"Inflammation and cell death during cholestasis: the evolving role of bile acids","volume":"19","author":"Woolbright","year":"2019","journal-title":"Gene Expr"},{"key":"10.1016\/j.jhep.2022.05.044_bib2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/liv.13306","article-title":"Management of cholestatic disease in 2017","volume":"37","author":"de Vries","year":"2017","journal-title":"Liver Int"},{"key":"10.1016\/j.jhep.2022.05.044_bib3","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.jhep.2018.08.020","article-title":"Primary biliary cholangitis: a tale of epigenetically-induced secretory failure?","volume":"69","author":"Rodrigues","year":"2018","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.05.044_bib4","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.clinre.2011.04.007","article-title":"Current consensus on the management of primary sclerosing cholangitis","volume":"35","author":"Wiencke","year":"2011","journal-title":"Clin Res Hepatol Gastroenterol"},{"key":"10.1016\/j.jhep.2022.05.044_bib5","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1146\/annurev-pharmtox-010818-021059","article-title":"Drug therapies for chronic cholestatic liver diseases","volume":"60","author":"Wagner","year":"2020","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"10.1016\/j.jhep.2022.05.044_bib6","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.ajpath.2014.10.009","article-title":"The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats","volume":"185","author":"Verbeke","year":"2015","journal-title":"Am J Pathol"},{"key":"10.1016\/j.jhep.2022.05.044_bib7","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41575-019-0125-y","article-title":"Cholangiocyte pathobiology","volume":"16","author":"Banales","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.jhep.2022.05.044_bib8","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/hep.30150","article-title":"Ductular reaction in liver diseases: pathological mechanisms and translational significances","volume":"69","author":"Sato","year":"2019","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.05.044_bib9","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1111\/liv.14153","article-title":"The gut microbial influence on cholestatic liver disease","volume":"39","author":"Kummen","year":"2019","journal-title":"Liver Int"},{"key":"10.1016\/j.jhep.2022.05.044_bib10","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1136\/gutjnl-2015-311004","article-title":"Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD","volume":"65","author":"Sabino","year":"2016","journal-title":"Gut"},{"key":"10.1016\/j.jhep.2022.05.044_bib11","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1136\/gutjnl-2016-313332","article-title":"Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy","volume":"67","author":"Tang","year":"2018","journal-title":"Gut"},{"key":"10.1016\/j.jhep.2022.05.044_bib12","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1113\/jphysiol.2011.219691","article-title":"Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut","volume":"590","author":"Seki","year":"2012","journal-title":"J\u00a0Physiol"},{"key":"10.1016\/j.jhep.2022.05.044_bib13","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.imbio.2008.07.008","article-title":"From expression to signaling: roles of TREM-1 and TREM-2 in innate immunity and bacterial infection","volume":"213","author":"Sharif","year":"2008","journal-title":"Immunobiology"},{"key":"10.1016\/j.jhep.2022.05.044_bib14","doi-asserted-by":"crossref","first-page":"4334","DOI":"10.1074\/jbc.R115.704981","article-title":"The triggering receptor expressed on myeloid cells 2: a molecular link of neuroinflammation and neurodegenerative diseases","volume":"291","author":"Walter","year":"2016","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.jhep.2022.05.044_bib15","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.jmb.2017.04.004","article-title":"TREM2-Ligand interactions in health and disease","volume":"429","author":"Kober","year":"2017","journal-title":"J\u00a0Mol Biol"},{"key":"10.1016\/j.jhep.2022.05.044_bib16","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1136\/gutjnl-2017-314107","article-title":"Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage","volume":"68","author":"Perugorria","year":"2019","journal-title":"Gut"},{"key":"10.1016\/j.jhep.2022.05.044_bib17","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1136\/gutjnl-2019-319227","article-title":"TREM-2 defends the liver against hepatocellular carcinoma through multifactorial protective mechanisms","volume":"70","author":"Esparza-Baquer","year":"2021","journal-title":"Gut"},{"key":"10.1016\/j.jhep.2022.05.044_bib18","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.4049\/jimmunol.177.6.3520","article-title":"Cutting edge: TREM-2 attenuates macrophage activation","volume":"177","author":"Turnbull","year":"2006","journal-title":"J\u00a0Immunol"},{"key":"10.1016\/j.jhep.2022.05.044_bib19","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/nm1663","article-title":"TLR4 enhances TGF-beta signaling and hepatic fibrosis","volume":"13","author":"Seki","year":"2007","journal-title":"Nat Med"},{"key":"10.1016\/j.jhep.2022.05.044_bib20","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1002\/hep.26108","article-title":"Tumor progression locus 2\/Cot is required for activation of extracellular regulated kinase in liver injury and toll-like receptor-induced TIMP-1 gene transcription in hepatic stellate cells in mice","volume":"57","author":"Perugorria","year":"2013","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.05.044_bib21","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/hep.23403","article-title":"Bicarbonate secretion of mouse cholangiocytes involves na-hco3 cotransport in addition to na-independent cl\/hco3 exchange","volume":"51","author":"Uriarte","year":"2010","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.05.044_bib22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ebiom.2016.11.021","article-title":"Early molecular stratification of high-risk primary biliary cholangitis","volume":"14","author":"Hardie","year":"2016","journal-title":"EBioMedicine"},{"key":"10.1016\/j.jhep.2022.05.044_bib23","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/s12276-021-00634-7","article-title":"Necroptosis molecular mechanisms: Recent findings regarding novel necroptosis regulators","volume":"53","author":"Seo","year":"2021","journal-title":"Exp Mol Med"},{"key":"10.1016\/j.jhep.2022.05.044_bib24","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2016.280","article-title":"Activation of necroptosis in human and experimental cholestasis","volume":"7","author":"Afonso","year":"2016","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.jhep.2022.05.044_bib25","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1053\/j.gastro.2014.07.018","article-title":"Cell death and cell death responses in liver disease: mechanisms and clinical relevance","volume":"147","author":"Luedde","year":"2014","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhep.2022.05.044_bib26","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41575-019-0226-7","article-title":"Primary biliary cholangitis: pathogenesis and therapeutic opportunities","volume":"17","author":"Gulamhusein","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.jhep.2022.05.044_bib27","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1023\/A:1020511002025","article-title":"Cytokine profile in the liver of primary biliary cirrhosis","volume":"19","author":"Nagano","year":"1999","journal-title":"J\u00a0Clin Immunol"},{"key":"10.1016\/j.jhep.2022.05.044_bib28","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1002\/hep.26993","article-title":"Cholangiocyte senescence by way of N-Ras activation is a characteristic of primary sclerosing cholangitis","volume":"59","author":"Tabibian","year":"2014","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.05.044_bib29","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jhep.2007.03.012","article-title":"Altered expression of TLR homolog RP105 on monocytes hypersensitive to LPS in patients with primary biliary cirrhosis","volume":"47","author":"Honda","year":"2007","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.05.044_bib30","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1620\/tjem.234.255","article-title":"Interleukin-33 promotes disease progression in patients with primary biliary cirrhosis","volume":"234","author":"Sun","year":"2014","journal-title":"Tohoku J Exp Med"},{"key":"10.1016\/j.jhep.2022.05.044_bib31","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1172\/JCI73742","article-title":"Biliary repair and carcinogenesis are mediated by IL-33-dependent cholangiocyte proliferation","volume":"124","author":"Li","year":"2014","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jhep.2022.05.044_bib32","doi-asserted-by":"crossref","first-page":"G773","DOI":"10.1152\/ajpgi.00080.2019","article-title":"Cell-specific regulatory effects of CXCR2 on cholestatic liver injury","volume":"317","author":"Konishi","year":"2019","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.jhep.2022.05.044_bib33","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41586-019-1631-3","article-title":"Resolving the fibrotic niche of human liver cirrhosis at single-cell level","volume":"575","author":"Ramachandran","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.jhep.2022.05.044_bib34","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.molcel.2019.07.028","article-title":"Landscape of intercellular crosstalk in healthy and NASH liver revealed by single-cell secretome gene analysis","volume":"75","author":"Xiong","year":"2019","journal-title":"Mol Cell"},{"key":"10.1016\/j.jhep.2022.05.044_bib35","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1002\/hep.31228","article-title":"Intestinal microbiome-macrophage crosstalk contributes to cholestatic liver disease by promoting intestinal permeability in mice","volume":"72","author":"Isaacs-Ten","year":"2020","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.05.044_bib36","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/hep.20603","article-title":"Contribution of Toll-like receptor\/myeloid differentiation factor 88 signaling to murine liver regeneration","volume":"41","author":"Seki","year":"2005","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.05.044_bib37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0197836","article-title":"Anti-inflammatory properties of ursodeoxycholyl lysophosphatidylethanolamide in endotoxin-mediated inflammatory liver injury","volume":"13","author":"Ludwig","year":"2018","journal-title":"PLoS One"}],"container-title":["Journal of Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168827822003725?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168827822003725?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T19:49:05Z","timestamp":1759175345000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168827822003725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["S0168827822003725"],"URL":"https:\/\/doi.org\/10.1016\/j.jhep.2022.05.044","relation":{},"ISSN":["0168-8278"],"issn-type":[{"value":"0168-8278","type":"print"}],"subject":[],"published":{"date-parts":[[2022,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"TREM-2 plays a protective role in cholestasis by acting as a negative regulator of inflammation","name":"articletitle","label":"Article Title"},{"value":"Journal of Hepatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jhep.2022.05.044","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.","name":"copyright","label":"Copyright"}]}}