CD141+ myeloid dendritic cells are enriched in healthy human liver

Kelly, Aoife; Fahey, Ronan; Fletcher, Jean M.; Keogh, Catherine; Carroll, Anne G.; Siddachari, Ravichand; Geoghegan, Justin; Hegarty, John E.; Ryan, Eleanor; O’Farrelly, Cliona

doi:10.1016/j.jhep.2013.08.007

Cited by 85 publications

(80 citation statements)

References 25 publications

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“…Liver dendritic cells Ten papers describe the immunophenotype of liver dendritic cells (DC) in human liver [20,51,95,[97][98][99][100][101][102][103].…”

Section: Heterogeneitymentioning

confidence: 99%

“…Further to studies of liver tissue from biopsy samples, liver perfusates from liver transplant procedures have described CD141 expressing DCs that appear to be of a more pro-inflammatory phenotype than CD14 + and CD1c + MPS in the liver [102]. However, it is apparent that CD141 is much more widely expressed in liver cells than in blood, where it is largely restricted to CLEC9A + DC [111].…”

Section: Heterogeneitymentioning

confidence: 99%

See 1 more Smart Citation

The immunophenotype of antigen presenting cells of the mononuclear phagocyte system in normal human liver – A systematic review

Strauß

Dunbar

Bartlett

et al. 2015

Journal of Hepatology

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The mononuclear phagocytic system (MPS), comprised of monocytes, macrophages, and dendritic cells, is essential in tissue homeostasis and in determining the balance of the immune response through its role in antigen presentation. It has been identified as a therapeutic target in infectious disease, cancer, autoimmune disease and transplant rejection. Here, we review the current understanding of the immunophenotype and function of the MPS in normal human liver. Using well-defined selection criteria, a search of MEDLINE and EMBASE databases identified 76 appropriate studies. The majority (n=67) described Kupffer cells (KCs), although the definition of KC differs between sources, and little data were available regarding their function. Only 10 papers looked at liver dendritic cells (DCs), and largely confirmed the presence of the major dendritic cell subsets identified in human blood. Monocytes were thoroughly characterized in four studies that utilized flow cytometry and fluorescent microscopy and highlighted their prominent role in liver homeostasis and displayed subtle differences from circulating monocytes. There was some limited evidence that liver DCs are tolerogenic but neither liver dendritic cell subsets nor macrophages have been thoroughly characterized, using either multi-colour flow cytometry or multi-parameter fluorescence microscopy. The lobular distribution of different subsets of liver MPS cells was also poorly described, and the ability to distinguish between passenger leukocytes and tissue resident cells remains limited. It was apparent that further research, using modern immunological techniques, is now required to accurately characterize the cells of the MPS in human liver.

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“…Liver dendritic cells Ten papers describe the immunophenotype of liver dendritic cells (DC) in human liver [20,51,95,[97][98][99][100][101][102][103].…”

Section: Heterogeneitymentioning

confidence: 99%

Section: Heterogeneitymentioning

confidence: 99%

The immunophenotype of antigen presenting cells of the mononuclear phagocyte system in normal human liver – A systematic review

Strauß

Dunbar

Bartlett

et al. 2015

Journal of Hepatology

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“…Our own laboratory has shown that chronic inflammatory liver disease in humans is associated with the hepatic enrichment of myeloid DCs, in both HCV+ and HCV− subjects(4). Another recent study, which included healthy subjects, also documented an enrichment of pro-inflammatory CD141+ DCs within the liver circulation compared to peripheral blood, suggesting that myeloid cells may have a yet-to-be defined role in immune surveillance even at steady state(5). How these cells are recruited or influenced within the liver is not well understood in humans.…”

Section: Introductionmentioning

confidence: 99%

Systems biological analyses reveal the hepatitis C virus (HCV)‐specific regulation of hematopoietic development

et al. 2015

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Chronic liver disease is characterized by the liver enrichment of myeloid DCs. To assess the role of disease on myelopoiesis, we utilized a systems biology approach to study development in liver-resident cells expressing stem cell marker CD34. In patients with end-stage liver disease, liver CD34+ cells were comprised by two subsets, designated CD34+CD146+ and CD34+CD146−, and hematopoietic function was restricted to CD34+CD146− cells. Liver CD34 frequencies were reduced during nonalcoholic steatohepatitis (NASH) and chronic hepatitis C virus (HCV) compared to alcohol liver disease (ALD), and this reduction correlated with viral load in the HCV cohort. To better understand the relationship between liver CD34+CD146+ and CD34+CD146− subsets and any effects of disease on CD34 development, we used gene expression profiling and computational modeling to compare each subset during ALD and HCV. For CD34+CD146+ cells, increased expression of endothelial cell genes including von Willebrand factor, VE-cadherin and eNOS were observed when compared to CD34+CD146− cells, and minimal effects of ALD and HCV diseases on gene expression were observed. Importantly for CD34+CD146− cells, chronic HCV was associated with a distinct ‘imprint’ of programs related to cell cycle, DNA repair, chemotaxis, development, and activation, with an emphasis on myeloid and B lymphocyte lineages. This HCV signature was further translated in side-by-side analyses, where HCV CD34+CD146− cells demonstrated superior hematopoietic growth, colony formation, and diversification compared to ALD and NASH when cultured identically. Disease-associated effects on hematopoiesis were also evident by phenotypic alterations in the expression of CD14, HLA-DR and CD16 by myeloid progeny cells. Conclusion Etiology drives progenitor fate within diseased tissues. The liver may be a useful source of hematopoietic cells for therapy, or as therapeutic targets.

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“…DC numbers are [12, 16, 19, 31, 33, 42, 55, 85-87, 89, 100, 133-135, 144, 147-151, 162] Human dendritic cell subsets and function in health and disease enriched in human liver [39,40]. Although whether their numbers increase or decrease in liver disease is currently under debate [39][40][41], it is clear that lung and bloodderived CD141 ? DC are major producers of IFN-III in response to HCV or polyinosinic:polycytidylic acid (poly I:C) [33,39,40].…”

Section: Human Dendritic Cellsmentioning

confidence: 99%

“…Although whether their numbers increase or decrease in liver disease is currently under debate [39][40][41], it is clear that lung and bloodderived CD141 ? DC are major producers of IFN-III in response to HCV or polyinosinic:polycytidylic acid (poly I:C) [33,39,40]. Thus, CD141 ?…”

Section: Human Dendritic Cellsmentioning

confidence: 99%

Human dendritic cell subsets and function in health and disease

O’Keeffe

Mok

Radford

2015

Cell. Mol. Life Sci.

165

149

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The method of choice for the development of new vaccines is to target distinct dendritic cell subsets with antigen in vivo and to harness their function in situ to enhance cell-mediated immunity or induce tolerance to specific antigens. The innate functions of dendritic cells themselves may also be targeted by inhibitors or activators that would target a specific function such as interferon production, potentially important in autoimmune disease and chronic viral infections. Importantly targeting dendritic cells requires detailed knowledge of both the surface phenotype and function of each dendritic cell subset, including how they may respond to different types of vaccine adjuvants, their ability to produce soluble mediators and to process and present antigens and induce priming of naïve T cells. This review summarizes our knowledge of the functional attributes of the human dendritic cell subsets in the steady state and upon activation and their roles in human disease.

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CD141+ myeloid dendritic cells are enriched in healthy human liver

Cited by 85 publications

References 25 publications

The immunophenotype of antigen presenting cells of the mononuclear phagocyte system in normal human liver – A systematic review

The immunophenotype of antigen presenting cells of the mononuclear phagocyte system in normal human liver – A systematic review

Systems biological analyses reveal the hepatitis C virus (HCV)‐specific regulation of hematopoietic development

Human dendritic cell subsets and function in health and disease

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