{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:15:18Z","timestamp":1787015718111,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T00:00:00Z","timestamp":1578441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["323530\u2010151477"],"award-info":[{"award-number":["323530\u2010151477"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["PP00P3_139021"],"award-info":[{"award-number":["PP00P3_139021"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003360","name":"Ligue Genevoise Contre le Cancer","doi-asserted-by":"publisher","award":["1509"],"award-info":[{"award-number":["1509"]}],"id":[{"id":"10.13039\/501100003360","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010768","name":"Fondation Art\u00e8res","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010768","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>Our understanding of non\u2010alcoholic fatty liver disease (NAFLD) pathogenesis is improving, but there is still limited data on the function of resident liver macrophages in this context, especially when considering their contribution in dampening liver inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Liver macrophages were studied in mouse models of prolonged diet\u2010induced liver steatohepatitis and carbon tetrachloride\u2010induced liver injury. We assessed liver macrophages phenotype and costimulatory\/inhibitory properties upon exposure to lipopolysaccharide or interleukin 4. We did phagocytosis and antigen presentation assays to investigate liver macrophages function as scavengers and immune response initiators. Using immunofluorescence staining, we further determined, in human liver tissue of patients with simple steatosis, non\u2010alcoholic steatohepatitis and chronic hepatitis B infection, the expression of the co\u2010inhibitory protein CD274 (Programmed\u2010death ligand 1) and major histocompatibility complex (MHC) class II.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both in humans and mice, within chronically inflamed fatty livers, liver macrophages acquired immunomodulatory properties by reducing the expression of MHC class II, and by enhancing co\u2010inhibitory signalling. Liver macrophages circumscribed endotoxin\u2010mediated inflammatory response by upregulating anti\u2010inflammatory genes arginase 1 and interleukin\u201010. While hepatic macrophages isolated from mice with normal livers were capable of achieving endotoxin tolerance, our results indicated an impairment of this protective mechanism in the presence NASH\u2010like parenchymal abnormalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Liver macrophages can achieve endotoxin tolerance, but in the chronically inflamed fatty liver, while they acquire an immunomodulatory phenotype, liver macrophages fail to dampen immune\u2010mediated damage. Therefore, loss of tolerogenicity induced by ongoing liver insult may be a mechanism contributing to the worsening of NAFLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.14336","type":"journal-article","created":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T01:25:41Z","timestamp":1577150741000},"page":"609-621","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Tolerogenic properties of liver macrophages in non\u2010alcoholic steatohepatitis"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7540-198X","authenticated-orcid":false,"given":"Lorenzo A.","family":"Orci","sequence":"first","affiliation":[{"name":"Division of Abdominal and Transplantation Surgery Department of Surgery Faculty of Medicine Geneva University Hospitals Geneva Switzerland"},{"name":"Hepato\u2010pancreato\u2010biliary centre Faculty of Medicine Geneva University Hospitals Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0335-2733","authenticated-orcid":false,"given":"Mario","family":"Kreutzfeldt","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology University of Geneva Geneva Switzerland"},{"name":"Division of Clinical Pathology Geneva University Hospital Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8698-4690","authenticated-orcid":false,"given":"Nicolas","family":"Goossens","sequence":"additional","affiliation":[{"name":"Hepato\u2010pancreato\u2010biliary centre Faculty of Medicine Geneva University Hospitals Geneva Switzerland"},{"name":"Division of Gastroenterology and Hepatology Department of Medicine Faculty of Medicine Geneva University Hospitals Geneva 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Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8931-0977","authenticated-orcid":false,"given":"Vaihere","family":"Delaune","sequence":"additional","affiliation":[{"name":"Division of Abdominal and Transplantation Surgery Department of Surgery Faculty of Medicine Geneva University Hospitals Geneva Switzerland"},{"name":"Hepato\u2010pancreato\u2010biliary centre Faculty of Medicine Geneva University Hospitals Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6637-0675","authenticated-orcid":false,"given":"Graziano","family":"Oldani","sequence":"additional","affiliation":[{"name":"Division of Abdominal and Transplantation Surgery Department of Surgery Faculty of Medicine Geneva University Hospitals Geneva Switzerland"},{"name":"Hepato\u2010pancreato\u2010biliary centre Faculty of Medicine Geneva University Hospitals Geneva 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