{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T21:44:07Z","timestamp":1789163047857,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T00:00:00Z","timestamp":1589500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI16\/967"],"award-info":[{"award-number":["PI16\/967"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["PROMETEO 2016\/001"],"award-info":[{"award-number":["PROMETEO 2016\/001"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatic immune function is compromised during cirrhosis. This study investigated the immune features of liver sinusoidal endothelial cells (LSECs) in two experimental models of cirrhosis. Dendritic cells, hepatic macrophages, and LSECs were isolated from carbon tetrachloride and bile duct-ligated rats. Gene expression of innate receptors, bacterial internalization, co-stimulatory molecules induction, and CD4+ T cell activation and differentiation were evaluated. Induced bacterial peritonitis and norfloxacin protocols on cirrhotic rats were also carried out. LSECs demonstrated an active immunosurveillance profile, as shown by transcriptional modulation of different scavenger and cell-adhesion genes, and their contribution to bacterial internalization. LSECs significantly increased their expression of CD40 and CD80 and stimulated CD4+ T cell activation marker CD71 in both models. The pro-inflammatory Th17 subset was expanded in CCl4-derived LSECs co-cultures. In the bile duct ligation (BDL) model, CD4+ T cell differentiation only occurred under induced bacterial peritonitis conditions. Differentiated pro-inflammatory Th cells by LSECs in both experimental models were significantly reduced with norfloxacin treatment, whereas Foxp3 tolerogenic Th CD4+ cells were expanded. Conclusion: LSECs\u2019 participation in the innate-adaptive immune progression, their ability to stimulate pro-inflammatory CD4+ T cells expansion during liver damage, and their target role in norfloxacin-induced immunomodulation granted a specific competence to this cell population in cirrhosis.<\/jats:p>","DOI":"10.3390\/cells9051227","type":"journal-article","created":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T10:53:59Z","timestamp":1589540039000},"page":"1227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Liver Sinusoidal Endothelial Cells Contribute to Hepatic Antigen-Presenting Cell Function and Th17 Expansion in Cirrhosis"],"prefix":"10.3390","volume":"9","author":[{"given":"Esther","family":"Caparr\u00f3s","sequence":"first","affiliation":[{"name":"Departamento Medicina Cl\u00ednica, Universidad Miguel Hern\u00e1ndez, 03550 San Juan de Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriol","family":"Juanola","sequence":"additional","affiliation":[{"name":"Departamento Medicina Cl\u00ednica, Universidad Miguel Hern\u00e1ndez, 03550 San Juan de Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"G\u00f3mez-Hurtado","sequence":"additional","affiliation":[{"name":"CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaya","family":"Puig-Kroger","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM), Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Pi\u00f1ero","sequence":"additional","affiliation":[{"name":"Instituto ISABIAL, Hospital General Universitario Alicante, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7927-858X","authenticated-orcid":false,"given":"Pedro","family":"Zapater","sequence":"additional","affiliation":[{"name":"CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto ISABIAL, Hospital General Universitario Alicante, 03010 Alicante, Spain"},{"name":"Departamento Farmacolog\u00eda, Universidad Miguel Hern\u00e1ndez, 03550 San Juan de Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Linares","sequence":"additional","affiliation":[{"name":"Departamento Medicina Cl\u00ednica, Universidad Miguel Hern\u00e1ndez, 03550 San Juan de Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabi\u00e1n","family":"Tar\u00edn","sequence":"additional","affiliation":[{"name":"Instituto ISABIAL, Hospital General Universitario Alicante, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1720-845X","authenticated-orcid":false,"given":"Sebasti\u00e1n","family":"Mart\u00ednez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Departamento Medicina Cl\u00ednica, Universidad Miguel Hern\u00e1ndez, 03550 San Juan de Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-4089","authenticated-orcid":false,"given":"Jordi","family":"Gracia-Sancho","sequence":"additional","affiliation":[{"name":"CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto de Investigaciones Biom\u00e9dicas August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Gonz\u00e1lez-Navajas","sequence":"additional","affiliation":[{"name":"CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto ISABIAL, Hospital General Universitario Alicante, 03010 Alicante, Spain"},{"name":"Departamento Farmacolog\u00eda, Universidad Miguel Hern\u00e1ndez, 03550 San Juan de Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5105-1201","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Franc\u00e9s","sequence":"additional","affiliation":[{"name":"Departamento Medicina Cl\u00ednica, Universidad Miguel Hern\u00e1ndez, 03550 San Juan de Alicante, Spain"},{"name":"CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto ISABIAL, Hospital General Universitario Alicante, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.jhep.2014.08.010","article-title":"Cirrhosis-associated immune dysfunction: Distinctive features and clinical relevance","volume":"61","author":"Albillos","year":"2014","journal-title":"J. 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