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

Bidirectional transendothelial migration of monocytes across hepatic sinusoidal endothelium shapes monocyte differentiation and regulates the balance between immunity and tolerance in liver.
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单核细胞跨肝窦内皮形状的单核细胞的双向跨内皮迁移,可以调节肝脏免疫和耐受性之间的平衡。

DOI:
10.1002/hep.28285
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发表时间:
2016-01
期刊:
Hepatology (Baltimore, Md.)
影响因子:
--
通讯作者:
Adams DH
Adams DH
中科院分区:
其他
文献类型:
--
作者:
Zimmermann HW;Bruns T;Weston CJ;Curbishley SM;Liaskou E;Li KK;Resheq YJ;Badenhorst PW;Adams DH

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单核细胞是一种多功能细胞,当被招募到肝脏时,它可以发挥促炎和抗炎功能。募集的单核细胞分化为组织巨噬细胞和树突状细胞,它们采集抗原并迁移到淋巴结引起t细胞反应。决定单核细胞分化的信号和肝窦内皮细胞(HSEC)在这一过程中的作用尚不清楚。已知HSEC可以调节t细胞活化,因此我们研究了单核细胞跨HSEC的跨内皮迁移(TEM)是否会影响它们的表型和功能。血源性单核细胞亚群可以通过人造血干细胞转移到胶原基质中。大多数迁移的细胞停留在内皮下基质中,但约10%的细胞发生自发的基底到根尖透射电镜。比较了逆行单核细胞(RT)和内皮下单核细胞(SE)的成熟程度、细胞因子分泌和t细胞刺激能力。se -单核细胞以CD16-为主,而75-80%的rt -单核细胞为CD16+。se单核细胞来源于CD14++CD16−亚群,表现出高吞噬活性,而rt单核细胞来源于CD14++CD16+和CD14+CD16++单核细胞,表现出不成熟的dc样表型(CD11cposHLA-DRposCD80loCD86lo),表达更高水平的CCR8。与dc表型一致的是,rt单核细胞分泌炎症细胞因子并诱导ag特异性CD4+ t细胞活化。相反,硒单核细胞抑制t细胞的增殖和活化,并表现出内毒素耐受性。转录组分析强调了SE和rt单核细胞之间的功能差异。跨越HSEC的迁移塑造了单核细胞随后的命运,从而在组织中产生无能巨噬细胞样细胞,并将免疫能力强的前dc释放到循环中。
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 transendothelial migration (TEM) of monocytes across HSEC influences their phenotype and function. Subsets of blood-derived monocytes were allowed to transmigrate across human HSEC into a collagen matrix. Most migrated cells remained in the subendothelial matrix but ~10% underwent spontaneous basal to apical TEM. 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 DC-like phenotype (CD11cposHLA-DRposCD80loCD86lo) and expressed higher levels of CCR8. Consistent with a DC-phenotype RT-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 RT-monocytes. 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.
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发表时间: 2011-02
期刊: HEPATOLOGY
影响因子: 13.5
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发表时间: 2009-02-15
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
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