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Hepatology. 2016 Jan;63(1):233-46. doi: 10.1002/hep.28285. Epub 2015 Nov 23.

Bidirectional transendothelial migration of monocytes across hepatic sinusoidal endothelium shapes monocyte differentiation and regulates the balance between immunity and tolerance in liver.

Author information

1
National Institute for Health Research Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK.
2
Department of Medicine III, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
3
Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany.
4
Center for Sepsis Control and Care, Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany.
5
Department of Internal Medicine 5, Hematology and Oncology, University of Erlangen-Nuremberg, Erlangen, Germany.
6
School of Immunity and Infection, University of Birmingham, Birmingham, UK.

Abstract

Monocytes are versatile cells that can fulfill proinflammatory and anti-inflammatory functions when recruited to the liver. Recruited monocytes differentiate into tissue macrophages and dendritic cells, which sample antigens and migrate to lymph nodes to elicit T-cell responses. The signals that determine monocyte differentiation and the role of hepatic sinusoidal endothelial cells (HSECs) in this process are poorly understood. HSECs are known to modulate T-cell activation, which led us to investigate whether transendothelial migration of monocytes across HSECs influences their phenotype and function. Subsets of blood-derived monocytes were allowed to transmigrate across human HSECs into a collagen matrix. Most migrated cells remained in the subendothelial matrix, but ~10% underwent spontaneous basal to apical transendothelial migration. The maturation, cytokine secretion, and T-cell stimulatory capacity of reverse transmigrating (RT) and subendothelial (SE) monocytes were compared. SE monocytes were mainly CD16(-) , whereas 75%-80% of RT monocytes were CD16(+) . SE monocytes derived from the CD14(++) CD16(-) subset and exhibited high phagocytic activity, whereas RT monocytes originated from CD14(++) CD16(+) and CD14(+) CD16(++) monocytes, displayed an immature dendritic cell-like phenotype (CD11c(pos) HLA-DR(pos) CD80lo CD86lo ), and expressed higher levels of chemokine (C-C motif) receptor 8. Consistent with a dendritic cell phenotype, RT monocytes secreted inflammatory cytokines and induced antigen-specific CD4(+) T-cell activation. In contrast, SE monocytes suppressed T-cell proliferation and activation and exhibited endotoxin tolerance. Transcriptome analysis underscored the functional differences between SE and RT monocytes.

CONCLUSIONS:

Migration across HSECs shapes the subsequent fate of monocytes, giving rise to anergic macrophage-like cells in tissue and the release of immunocompetent pre-dendritic cells into the circulation.

PMID:
26473398
DOI:
10.1002/hep.28285
[Indexed for MEDLINE]
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