PMID- 23968887 OWN - NLM STAT- MEDLINE DCOM- 20140926 LR - 20220317 IS - 1600-0641 (Electronic) IS - 0168-8278 (Linking) VI - 60 IP - 1 DP - 2014 Jan TI - CD141(+) myeloid dendritic cells are enriched in healthy human liver. PG - 135-42 LID - S0168-8278(13)00592-8 [pii] LID - 10.1016/j.jhep.2013.08.007 [doi] AB - BACKGROUND & AIMS: Extensive populations of liver immune cells detect and respond to homeostatic perturbation caused by damage, infection or malignancy. Dendritic cells (DCs) are central to these activities, governing the balance between tolerance and immunity. Most of our knowledge about human liver DCs is derived from studies on peritumoral tissue. Little is known about the phenotype and function of DCs, in particular the recently described CD141(+) subset, in healthy human liver and how this profile is altered in liver disease. METHODS: During liver transplantation, healthy donor and diseased explant livers were perfused and hepatic mononuclear cells isolated. Dendritic cell subset frequency and phenotype were characterised in liver perfusates by flow cytometry and the function of CD141(+) DCs was evaluated by mixed lymphocyte reactions (MLRs) and measuring cytokine secretion. RESULTS: Almost one third of liver CD11c(+) myeloid DCs (mDCs) expressed CD141 compared to <5% of circulating mDCs. Hepatic CD141(+) DCs demonstrated pro-inflammatory function in allogeneic MLRs, inducing T cell production of interferon gamma (IFN-gamma) and interleukin (IL)-17. While CD123(+) plasmacytoid DCs (pDCs) and CD1c(+) mDCs were expanded in diseased liver perfusates, CD141(+) DCs were significantly depleted. Despite their depletion, CD141(+) DCs from explant livers produced markedly increased poly(I:C)-induced IFN lambda (IFN-lambda) compared with donor DCs. CONCLUSIONS: Accumulation of CD141(+) DCs in healthy liver, which are significantly depleted in liver disease, suggests differential involvement of mDC subsets in liver immunity. CI - Copyright (c) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. FAU - Kelly, Aoife AU - Kelly A AD - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. FAU - Fahey, Ronan AU - Fahey R AD - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. FAU - Fletcher, Jean M AU - Fletcher JM AD - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. FAU - Keogh, Catherine AU - Keogh C AD - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. FAU - Carroll, Anne G AU - Carroll AG AD - Department of Surgery, St. Vincent's University Hospital, Dublin 4, Ireland. FAU - Siddachari, Ravichand AU - Siddachari R AD - Department of Surgery, St. Vincent's University Hospital, Dublin 4, Ireland. FAU - Geoghegan, Justin AU - Geoghegan J AD - Department of Surgery, St. Vincent's University Hospital, Dublin 4, Ireland. FAU - Hegarty, John E AU - Hegarty JE AD - Liver Unit, St. Vincent's University Hospital, Dublin 4, Ireland. FAU - Ryan, Elizabeth J AU - Ryan EJ AD - Centre for Colorectal Disease, Education and Research Centre, St. Vincent's University Hospital, Dublin 4, Ireland; School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland. FAU - O'Farrelly, Cliona AU - O'Farrelly C AD - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. Electronic address: cliona.ofarrelly@tcd.ie. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130819 PL - Netherlands TA - J Hepatol JT - Journal of hepatology JID - 8503886 RN - 0 (Antigens, Surface) RN - 0 (CLEC9a protein, human) RN - 0 (LILRB2 protein, human) RN - 0 (LILRB4 protein, human) RN - 0 (Lectins, C-Type) RN - 0 (Membrane Glycoproteins) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, Mitogen) RN - 0 (THBD protein, human) RN - 0 (Thrombomodulin) SB - IM CIN - J Hepatol. 2014 Jan;60(1):9-11. PMID: 24140762 CIN - J Hepatol. 2014 May;60(5):1097-8. PMID: 24418015 CIN - J Hepatol. 2014 May;60(5):1098-9. PMID: 24418016 MH - Adolescent MH - Adult MH - Aged MH - Antigens, Surface/*analysis MH - Dendritic Cells/*immunology MH - Female MH - Humans MH - Lectins, C-Type/analysis MH - Liver/*immunology MH - Male MH - Membrane Glycoproteins/analysis MH - Middle Aged MH - Myeloid Cells/*immunology MH - Receptors, Cell Surface/analysis MH - Receptors, Immunologic/analysis MH - Receptors, Mitogen/analysis MH - Thrombomodulin OTO - NOTNLM OT - ALD OT - C-type lectin domain family 9 member A OT - CLEC9A OT - DCs OT - HCC OT - HCV OT - HMNCs OT - Hepatitis C virus OT - IFN-alpha OT - IFN-gamma OT - IFN-lambda OT - IL-17 OT - IL-29 OT - ILT OT - Liver perfusate OT - MLR OT - NASH OT - TLR OT - Toll-like receptor OT - UW OT - University of Wisconsin OT - alcoholic liver disease OT - dendritic cells OT - hepatic mononuclear cells OT - hepatitis C virus OT - hepatocellular carcinoma OT - immunoglobulin-like transcript OT - interferon alpha OT - interferon gamma OT - interferon lambda OT - interleukin 17 OT - mDCs OT - mixed lymphocyte reaction OT - myeloid dendritic cells OT - non-alcoholic steatohepatitis OT - pDCs OT - plasmacytoid dendritic cells OT - poly(I:C) EDAT- 2013/08/24 06:00 MHDA- 2014/09/27 06:00 CRDT- 2013/08/24 06:00 PHST- 2013/01/15 00:00 [received] PHST- 2013/08/04 00:00 [revised] PHST- 2013/08/05 00:00 [accepted] PHST- 2013/08/24 06:00 [entrez] PHST- 2013/08/24 06:00 [pubmed] PHST- 2014/09/27 06:00 [medline] AID - S0168-8278(13)00592-8 [pii] AID - 10.1016/j.jhep.2013.08.007 [doi] PST - ppublish SO - J Hepatol. 2014 Jan;60(1):135-42. doi: 10.1016/j.jhep.2013.08.007. Epub 2013 Aug 19.