{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:09:48Z","timestamp":1792804188594,"version":"4.5.0"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T00:00:00Z","timestamp":1568764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Foundation","award":["(DFG Ta434\/3-1, Ta434\/5-1 and SFB\/1382)"],"award-info":[{"award-number":["(DFG Ta434\/3-1, Ta434\/5-1 and SFB\/1382)"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of East Piedmont","award":["Fondi Ricerca Locale"],"award-info":[{"award-number":["Fondi Ricerca Locale"]}],"id":[{"id":"https:\/\/ror.org\/01e0ns064","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Recent evidence suggests that hepatic dendritic cells (HDCs) contribute to the evolution of chronic liver diseases. However, the HDC subsets involved and the mechanisms driving these responses are still poorly understood. In this study, we have investigated the role of the fractalkine receptor CX3CR1 in modulating monocyte-derived dendritic cell (moDC) differentiation during liver inflammation. The phenotype of HDC and functional relevance of CX3CR1 was assessed in mice following necro-inflammatory liver injury induced by the hepatotoxic agent carbon tetrachloride (CCl4) and in steatohepatitis caused by a methionine\/choline-deficient (MCD) diet. In both the experimental models, hepatic inflammation was associated with a massive expansion of CD11c+\/MHCIIhigh\/CD11b+ myeloid HDCs. These cells also expressed the monocyte markers Ly6C, chemokine (C-C Motif) receptor 2 (CCR2), F4\/80 and CD88, along with CX3CR1, allowing their tentative identification as moDCs. Mice defective in CX3CR1 showed a reduction in liver-moDC recruitment following CCl4 poisoning in parallel with a defective maturation of monocytes into moDCs. The lack of CX3CR1 also affected moDC differentiation from bone marrow myeloid cells induced by granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) in vitro. In wild-type mice, treatment with the CX3CR1 antagonist CX3-AT (150 \u00b5g, i.p.) 24 h after CCl4 administration reduced liver moDCS and significantly ameliorated hepatic injury and inflammation. Altogether, these results highlight the possible involvement of moDCs in promoting hepatic inflammation following liver injury and indicated a novel role of CX3CL1\/CX3CR1 dyad in driving the differentiation of hepatic moDCs.<\/jats:p>","DOI":"10.3390\/cells8091099","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T04:26:46Z","timestamp":1568780806000},"page":"1099","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["CX3CR1 Mediates the Development of Monocyte-Derived Dendritic Cells during Hepatic Inflammation"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0192-8199","authenticated-orcid":false,"given":"Salvatore","family":"Sutti","sequence":"first","affiliation":[{"name":"Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University \u201cAmedeo Avogadro\u201d of East Piedmont, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Bruzz\u00ec","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University \u201cAmedeo Avogadro\u201d of East Piedmont, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Heymann","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Charit\u00e9 University Medical Center Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Liepelt","sequence":"additional","affiliation":[{"name":"Department of Medicine III, RWTH-University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Krenkel","sequence":"additional","affiliation":[{"name":"Department of Medicine III, RWTH-University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Toscani","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University \u201cAmedeo Avogadro\u201d of East Piedmont, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naresh","family":"Ramavath","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University \u201cAmedeo Avogadro\u201d of East Piedmont, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2714-4744","authenticated-orcid":false,"given":"Diego","family":"Cotella","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University \u201cAmedeo Avogadro\u201d of East Piedmont, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4738-7049","authenticated-orcid":false,"given":"Emanuele","family":"Albano","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University \u201cAmedeo Avogadro\u201d of East Piedmont, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Tacke","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Charit\u00e9 University Medical Center Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nrgastro.2015.200","article-title":"Immunology in the liver-from homeostasis to disease","volume":"13","author":"Heymann","year":"2016","journal-title":"Nar. 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