CXCR3 Activation Promotes Lymphocyte Transendothelial Migration across Human Hepatic Endothelium under Fluid Flow

Curbishley, Stuart M.; Eksteen, Bertus; Gladue, Ronald P.; Lalor, Patricia F.; Adams, David H.

doi:10.1016/s0002-9440(10)62060-3

Cited by 120 publications

(149 citation statements)

References 57 publications

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“…They are in line with a previous investigation demonstrating transendothelial migration of lymphocytes promoted by CXC3 ligands bound on the surface of activated human hepatic endothelium. 40 In our model system, activated LSEC also enhance chemokine-driven transmigration, albeit not at higher rates than resting LSEC (data not shown). Preliminary observations suggest that LSEC activation might be crucial for antigen-dependent adhesion and transmigration, presumably because of increased major histocompatibility complex II expression (K.N., unpublished data, 2008).…”

Section: Discussionmentioning

confidence: 66%

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

et al. 2008

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Transmigration through the liver endothelium is a prerequisite for the homeostatic balance of intrahepatic T cells and a key regulator of inflammatory processes within the liver. Extravasation into the liver parenchyma is regulated by the distinct expression patterns of adhesion molecules and chemokines and their receptors on the lymphocyte and endothelial cell surface. In the present study, we investigated whether liver sinusoidal endothelial cells ( H omeostatic extravasation into the liver parenchyma and transmigration of T cells into sites of inflammation under pathological conditions such as hepatitis and cholangitis are mediated by multiple steps involving activation and firm adhesion followed by egress. The process is closely regulated by the distinct expression patterns of adhesion molecules and chemokines and their receptors on the cell surface. 1,2 Within the liver, lymphocyte adhesion, a prerequisite for transmigration, occurs mainly within the sinusoidal circulation. Thus, T cell immigration into the liver is presumed to happen predominantly via the sinusoids. 3 Liver sinusoidal endothelial cells (LSEC) lining the sinusoids form a morphologically and functionally distinct endothelium that lacks a basement membrane, fails to form tight junctions, and displays fenestrae grouped to sieve plates. 4 In contrast to other tissues, selectins are not necessary for the initial adhesion of leukocytes to the liver microvasculature. The

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Section: Discussionmentioning

confidence: 66%

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

et al. 2008

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“…Moreover, liver production of CXCL9 and CXCL10 has been associated with the infiltration of CXCR3-expressing T lymphocytes in individuals with chronic hepatitis C virus infections (47). Studies have also shown that CXCR3 activation promotes the transendothelial migration of effector T cells across hepatic endothelium in response to CXCR3 ligands (6). Together, these observations suggest a functional role for CXCR3 and its ligands in promoting T-lymphocyte migration into the liver.…”

mentioning

confidence: 82%

CXCR3-Dependent Recruitment of Antigen-Specific T Lymphocytes to the Liver during Murine Cytomegalovirus Infection

Hokeness

Deweerd

Munks

et al. 2007

J Virol

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“…Liver-infiltrating lymphocytes (LILs) were isolated from fresh liver tissue, as previously described (18,19). To maximize yield and viability, LIT regs were isolated immediately after explantation of livers from patients with various liver diseases, including alcoholic cirrhosis, nonalcoholic steatohepatitis, primary biliary cirrhosis (PBC), and autoimmune hepatitis (AIH).…”

Section: Liver-infiltrating Lymphocyte and Lit Reg Isolationmentioning

confidence: 99%

Distinct Roles for CCR4 and CXCR3 in the Recruitment and Positioning of Regulatory T Cells in the Inflamed Human Liver

Weston

Lalor

et al. 2010

The Journal of Immunology

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Regulatory T cells (Tregs) are found at sites of chronic inflammation where they mediate bystander and Ag-specific suppression of local immune responses. However, little is known about the molecular control of Treg recruitment into inflamed human tissues. We report that up to 18% of T cells in areas of inflammation in human liver disease are forkhead family transcriptional regulator box P3 (FoxP3)+ Tregs. We isolated CD4+CD25+CD127lowFoxP3+ Tregs from chronically inflamed human liver removed at transplantation; compared with blood-derived Tregs, liver-derived Tregs express high levels of the chemokine receptors CXCR3 and CCR4. In flow-based adhesion assays using human hepatic sinusoidal endothelium, Tregs used CXCR3 and α4β1 to bind and transmigrate, whereas CCR4 played no role. The CCR4 ligands CCL17 and CCL22 were absent from healthy liver, but they were detected in chronically inflamed liver where their expression was restricted to dendritic cells (DCs) within inflammatory infiltrates. These DCs were closely associated with CD8 T cells and CCR4+ Tregs in the parenchyma and septal areas. Ex vivo, liver-derived Tregs migrated to CCR4 ligands secreted by intrahepatic DCs. We propose that CXCR3 mediates the recruitment of Tregs via hepatic sinusoidal endothelium and that CCR4 ligands secreted by DCs recruit Tregs to sites of inflammation in patients with chronic hepatitis. Thus, different chemokine receptors play distinct roles in the recruitment and positioning of Tregs at sites of hepatitis in chronic liver disease.

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CXCR3 Activation Promotes Lymphocyte Transendothelial Migration across Human Hepatic Endothelium under Fluid Flow

Cited by 120 publications

References 57 publications

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

CXCR3-Dependent Recruitment of Antigen-Specific T Lymphocytes to the Liver during Murine Cytomegalovirus Infection

Distinct Roles for CCR4 and CXCR3 in the Recruitment and Positioning of Regulatory T Cells in the Inflamed Human Liver

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