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CD141⁺ myeloid dendritic cells are enriched in healthy human liver.
J Hepatol. 2014 Jan; 60(1):135-42.JH

Abstract

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-γ) 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-λ) 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.

Authors+Show Affiliations

School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.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.School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.Department of Surgery, St. Vincent's University Hospital, Dublin 4, Ireland.Department of Surgery, St. Vincent's University Hospital, Dublin 4, Ireland.Department of Surgery, St. Vincent's University Hospital, Dublin 4, Ireland.Liver Unit, St. Vincent's University Hospital, Dublin 4, Ireland.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23968887

Citation

Kelly, Aoife, et al. "CD141⁺ Myeloid Dendritic Cells Are Enriched in Healthy Human Liver." Journal of Hepatology, vol. 60, no. 1, 2014, pp. 135-42.
Kelly A, Fahey R, Fletcher JM, et al. CD141⁺ myeloid dendritic cells are enriched in healthy human liver. J Hepatol. 2014;60(1):135-42.
Kelly, A., Fahey, R., Fletcher, J. M., Keogh, C., Carroll, A. G., Siddachari, R., Geoghegan, J., Hegarty, J. E., Ryan, E. J., & O'Farrelly, C. (2014). CD141⁺ myeloid dendritic cells are enriched in healthy human liver. Journal of Hepatology, 60(1), 135-42. https://doi.org/10.1016/j.jhep.2013.08.007
Kelly A, et al. CD141⁺ Myeloid Dendritic Cells Are Enriched in Healthy Human Liver. J Hepatol. 2014;60(1):135-42. PubMed PMID: 23968887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD141⁺ myeloid dendritic cells are enriched in healthy human liver. AU - Kelly,Aoife, AU - Fahey,Ronan, AU - Fletcher,Jean M, AU - Keogh,Catherine, AU - Carroll,Anne G, AU - Siddachari,Ravichand, AU - Geoghegan,Justin, AU - Hegarty,John E, AU - Ryan,Elizabeth J, AU - O'Farrelly,Cliona, Y1 - 2013/08/19/ PY - 2013/01/15/received PY - 2013/08/04/revised PY - 2013/08/05/accepted PY - 2013/8/24/entrez PY - 2013/8/24/pubmed PY - 2014/9/27/medline KW - ALD KW - C-type lectin domain family 9 member A KW - CLEC9A KW - DCs KW - HCC KW - HCV KW - HMNCs KW - Hepatitis C virus KW - IFN-α KW - IFN-γ KW - IFN-λ KW - IL-17 KW - IL-29 KW - ILT KW - Liver perfusate KW - MLR KW - NASH KW - TLR KW - Toll-like receptor KW - UW KW - University of Wisconsin KW - alcoholic liver disease KW - dendritic cells KW - hepatic mononuclear cells KW - hepatitis C virus KW - hepatocellular carcinoma KW - immunoglobulin-like transcript KW - interferon alpha KW - interferon gamma KW - interferon lambda KW - interleukin 17 KW - mDCs KW - mixed lymphocyte reaction KW - myeloid dendritic cells KW - non-alcoholic steatohepatitis KW - pDCs KW - plasmacytoid dendritic cells KW - poly(I:C) SP - 135 EP - 42 JF - Journal of hepatology JO - J. Hepatol. VL - 60 IS - 1 N2 - 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-γ) 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-λ) 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. SN - 1600-0641 UR - https://www.unboundmedicine.com/medline/citation/23968887/CD141⁺_myeloid_dendritic_cells_are_enriched_in_healthy_human_liver_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(13)00592-8 DB - PRIME DP - Unbound Medicine ER -