BACKGROUND: Monocytes are versatile cells that can fulfil pro- 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 (HSEC) in this process are poorly understood. HSEC are known to modulate T-cell activation leading us to investigate whether @entity4222 ( @entity4222 ) of monocytes across HSEC influences their phenotype and function. MATERIALS AND METHODS: Subsets of blood-derived monocytes were allowed to transmigrate across @entity1 HSEC into a collagen matrix. Most migrated cells remained in the subendothelial matrix but    10% underwent spontaneous basal to apical @entity4222 . The maturation, cytokine secretion and T-cell stimulatory capacity of @entity16757 ( @entity16757 ) and subendothelial (SE) monocytes were compared. RESULTS: SE-monocytes were mainly @entity4071 (_) whereas 75-80% of @entity16757 -monocytes were @entity4071 (+) . SE-monocytes derived from the @entity5750 ++ @entity4071 - subset and exhibited high phagocytic activity whereas @entity16757 -monocytes originated from @entity5750 ++ @entity4071 + and @entity5750 + @entity4071 ++ monocytes, displayed an immature DC-like phenotype ( @entity2935 (pos) HLA-DR(pos) @entity7938 lo @entity2937 lo ) and expressed higher levels of @entity9235 . Consistent with a DC-phenotype @entity16757 -monocytes secreted inflammatory cytokines and induced Ag-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 @entity16757 -monocytes. CONCLUSIONS: Migration across HSEC shapes the subsequent fate of monocytes giving rise to anergic macrophage-like cells in tissue and the release of immunocompetent pre-DCs into the circulation. This article is protected by copyright. All rights reserved.

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

@entity1 :: ('9606', 'Species') :: ['human'] @entity2937 :: ('942', 'Gene') :: ['CD86'] @entity5750 :: ('929', 'Gene') :: ['CD14'] @entity4222 :: ('MESH:D014085', 'Disease') :: ['TEM', 'transendothelial migration'] @entity7938 :: ('941', 'Gene') :: ['CD80'] @entity4071 :: ('2214', 'Gene') :: ['CD16'] @entity9235 :: ('1237', 'Gene') :: ['CCR8'] @entity2935 :: ('3687', 'Gene') :: ['CD11c'] @entity16757 :: ('MESH:D054038', 'Disease') :: ['reverse transmigrating', 'RT']
@entity4222 :: (MESH:D014085,Disease) :: ['transendothelial migration']
