PMID- 31540356 OWN - NLM STAT- MEDLINE DCOM- 20200601 LR - 20200601 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 8 IP - 9 DP - 2019 Sep 18 TI - CX(3)CR1 Mediates the Development of Monocyte-Derived Dendritic Cells during Hepatic Inflammation. LID - 10.3390/cells8091099 [doi] LID - 1099 AB - 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 CX(3)CR1 in modulating monocyte-derived dendritic cell (moDC) differentiation during liver inflammation. The phenotype of HDC and functional relevance of CX(3)CR1 was assessed in mice following necro-inflammatory liver injury induced by the hepatotoxic agent carbon tetrachloride (CCl(4)) 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(+)/MHCII(high)/CD11b(+) myeloid HDCs. These cells also expressed the monocyte markers Ly6C, chemokine (C-C Motif) receptor 2 (CCR2), F4/80 and CD88, along with CX(3)CR1, allowing their tentative identification as moDCs. Mice defective in CX(3)CR1 showed a reduction in liver-moDC recruitment following CCl(4) poisoning in parallel with a defective maturation of monocytes into moDCs. The lack of CX(3)CR1 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 CX(3)CR1 antagonist CX3-AT (150 microg, i.p.) 24 h after CCl(4) administration reduced liver moDC(S) 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 CX(3)CL1/CX(3)CR1 dyad in driving the differentiation of hepatic moDCs. FAU - Sutti, Salvatore AU - Sutti S AUID- ORCID: 0000-0002-0192-8199 AD - Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University "Amedeo Avogadro" of East Piedmont, Via Solaroli 17, 28100 Novara, Italy. salvatore.sutti@med.uniupo.it. FAU - Bruzzi, Stefania AU - Bruzzi S AD - Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University "Amedeo Avogadro" of East Piedmont, Via Solaroli 17, 28100 Novara, Italy. bruzzi.stefania@hsr.it. FAU - Heymann, Felix AU - Heymann F AD - Department of Hepatology and Gastroenterology, Charite University Medical Center Berlin, 10117 Berlin, Germany. felix.heymann@googlemail.com. FAU - Liepelt, Anke AU - Liepelt A AD - Department of Medicine III, RWTH-University Hospital Aachen, 52074 Aachen, Germany. apfeiffer@ukaachen.de. FAU - Krenkel, Oliver AU - Krenkel O AD - Department of Medicine III, RWTH-University Hospital Aachen, 52074 Aachen, Germany. okrenkel@ukaachen.de. FAU - Toscani, Alberto AU - Toscani A AD - Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University "Amedeo Avogadro" of East Piedmont, Via Solaroli 17, 28100 Novara, Italy. alberto_toscani@outlook.it. FAU - Ramavath, Naresh Naik AU - Ramavath NN AD - Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University "Amedeo Avogadro" of East Piedmont, Via Solaroli 17, 28100 Novara, Italy. naresh.ramavath@uniupo.it. FAU - Cotella, Diego AU - Cotella D AUID- ORCID: 0000-0003-2714-4744 AD - Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University "Amedeo Avogadro" of East Piedmont, Via Solaroli 17, 28100 Novara, Italy. diego.cotella@med.uniupo.it. FAU - Albano, Emanuele AU - Albano E AUID- ORCID: 0000-0003-4738-7049 AD - Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University "Amedeo Avogadro" of East Piedmont, Via Solaroli 17, 28100 Novara, Italy. emanuele.albano@med.uniupo.it. FAU - Tacke, Frank AU - Tacke F AD - Department of Hepatology and Gastroenterology, Charite University Medical Center Berlin, 10117 Berlin, Germany. frank.tacke@charite.de. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190918 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (CX3C Chemokine Receptor 1) RN - 0 (Cx3cr1 protein, mouse) RN - CL2T97X0V0 (Carbon Tetrachloride) SB - IM MH - Animals MH - CX3C Chemokine Receptor 1/antagonists & inhibitors/*metabolism MH - Carbon Tetrachloride/administration & dosage MH - Cell Differentiation MH - Chemical and Drug Induced Liver Injury MH - Dendritic Cells/*chemistry/metabolism MH - Disease Models, Animal MH - Inflammation/chemically induced/*metabolism MH - Liver/*metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Monocytes/*chemistry/metabolism PMC - PMC6770190 OTO - NOTNLM OT - carbon tetrachloride OT - dendritic cells OT - fractalkine OT - liver injury COIS- The authors have no competing interests on the matter concerning the present manuscript. EDAT- 2019/09/22 06:00 MHDA- 2020/06/02 06:00 PMCR- 2019/09/01 CRDT- 2019/09/22 06:00 PHST- 2019/08/01 00:00 [received] PHST- 2019/09/05 00:00 [revised] PHST- 2019/09/14 00:00 [accepted] PHST- 2019/09/22 06:00 [entrez] PHST- 2019/09/22 06:00 [pubmed] PHST- 2020/06/02 06:00 [medline] PHST- 2019/09/01 00:00 [pmc-release] AID - cells8091099 [pii] AID - cells-08-01099 [pii] AID - 10.3390/cells8091099 [doi] PST - epublish SO - Cells. 2019 Sep 18;8(9):1099. doi: 10.3390/cells8091099.