Human liver myeloid dendritic cells maturate in vivo into effector DC with a poor allogeneic T-cell stimulatory capacity

Kwekkeboom, Jaap; Boor, Patrick P.C.; Sen, Emel; Kusters, Johannes G.; Drexhage, Hemmo A.; Jong, Esther C. de; Tilanus, Hugo W.; IJzermans, Jan N.M.; Metselaar, Herold J.

doi:10.1016/j.transproceed.2004.12.003

Cited by 8 publications

(8 citation statements)

References 8 publications

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“…The post‐LTX biopsies had been taken, on average, 12 (range: 6–24) days after transplantation, and did not show significant histological rejection activity [mean rejection activity index (RAI) score 2; range: [0–5]. CD1c mAb was used as a marker for both immature and mature liver MDC [4,16,18], and DC‐Lamp as a marker for mature MDC [19]. Figure 2a shows that CD1c bright MDC were located predominantly in portal fields, while CD68 + macrophages/monocytes were observed both in portal fields and parenchyma.…”

Section: Resultsmentioning

confidence: 99%

Impairment of circulating myeloid dendritic cells in immunosuppressed liver transplant recipients

Bosma¹,

Metselaar²,

Tra³

et al. 2007

Clinical and Experimental Immunology

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SummaryThe aim of the present study was to elucidate the impact of liver transplantation (LTX) on myeloid dendritic cell (MDC) homeostasis. We observed a threefold reduction of circulating CD1c + MDC immediately after LTX (n = 16; P < 0·01), and normalization between 3 and 12 months after LTX. This decline was not due to recruitment of MDC into the liver graft, as numbers of MDC in post-LTX liver graft biopsies were not increased compared to pre-LTX biopsies (n = 7). Moreover, no change in chemokine receptor expression on circulating MDC was observed, suggesting that their homing properties were not altered. Normalization of circulating MDC was associated with withdrawal of corticosteroid therapy, and not with changes in calcineurin inhibitor intake, indicating that corticosteroids are responsible for the observed changes in numbers of circulating MDC. During high-dose corticosteroid treatment early after LTX, circulating MDC showed a lowered maturation status with decreased expression of human leucocyte antigen D-related (HLA-DR) and CD86 compared to pre-LTX values (P < 0·01). However, when MDC from blood of LTX recipients were matured ex vivo, they up-regulated HLA-DR and co-stimulatory molecules to a comparable extent as MDC from healthy individuals. In addition, ex vivo matured MDC from both groups had equal allogeneic T cell stimulatory capacity. In conclusion, during the first months after LTX numbers and maturational status of circulating MDC are impaired significantly, probably due to a suppressive effect of corticosteroids on MDC. However, corticosteroid therapy does not imprint MDC with an intrinsic resistance to maturation stimuli.

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Section: Resultsmentioning

confidence: 99%

Impairment of circulating myeloid dendritic cells in immunosuppressed liver transplant recipients

Bosma¹,

Metselaar²,

Tra³

et al. 2007

Clinical and Experimental Immunology

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“…Kwekkeboom et al [108] found that compared to inguinal lymph node DCs, hepatic DCs were less capable of stimulating T cells, despite higher expression of HLA-DR, CD80, and CD86. Bamboat et al found increased production of Foxp3 + Treg cells and IL-4 producing T cells (associated with the humoral immune response [109]) that were difficult to re-activate if initially activated by hepatic DCs in comparison to blood-derived DCs.…”

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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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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“…Interestingly, DC isolated from human hepatic lymph nodes have also been characterized by high IL-10 production and low allogenic stimulatory capacity, compared to human inguinal lymph node DC. 67 Murine liver DC have also been described as less capable of stimulating T cells, compared to spleen DC. 68 This may be due in part to differences in subset composition.…”

Section: Immunoregulatory Function Of Nk Cellsmentioning

confidence: 99%

Regulation of NK Cell Repertoire and Function in the Liver

et al. 2011

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NK cells represent a large proportion of the lymphocyte population in the liver and are involved in early innate immunity to pathogen infection. As a result of liver endothelial cell fenestrations, parenchymal cells are not separated by a basal membrane, and thereby pathogen-infected hepatocytes are extensively capable of interacting with innate immune cells including NK cells. In addition, hepatic NK cells interact with surrounding DC and alter their differentiation and function. Recent studies reveal that NK cells exhibit a regulatory function that modulates T cell responses through their interaction with DC and/or direct effect on T cells. Thus, NK cells play a central role, not only in innate immunity, but also in shaping the adaptive immune response. During pathogen infection, there is a remarkable increase of hepatic NK cells, possibly due to the expansion of resident liver NK cells and/or recruitement of NK cells from the blood. The liver microenvironment is believed to modulate hepatic NK cell function through the induction of activating/inhibitory receptor expression and inflammatory cytokine secretion. Particularly, the liver maintains intrahepatic NK cells in a functionally hyporesponsive state compared to splenic NK cells: liver NK cells displayed a dampened IFN-γ response to IL-12/IL-18 stimulation. Notably, the liver contains a significant population of functionally hyporesponsive NK cells that express high levels of the inhibitory receptor NKG2A and lack expression of MHC class I-binding Ly49 receptors. Importantly, adoptively transferred splenic NK cells that migrate to the liver displayed phenotypic and functional changes, supporting a view that the liver environment modifies NK cell receptor expression and functional responsiveness. In this article, we will review studies on the regulation of NK cell repertoire and function in the hepatic environment and the impact of liver NK cell immunoregulatory function on influencing adaptive immunity.

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Human liver myeloid dendritic cells maturate in vivo into effector DC with a poor allogeneic T-cell stimulatory capacity

Cited by 8 publications

References 8 publications

Impairment of circulating myeloid dendritic cells in immunosuppressed liver transplant recipients

Impairment of circulating myeloid dendritic cells in immunosuppressed liver transplant recipients

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

Regulation of NK Cell Repertoire and Function in the Liver

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