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

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Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines. / Schrage, Arnhild; Wechsung, Katja; Neumann, Katrin; Schumann, Michael; Schulzke, Jörg-Dieter; Engelhardt, Britta; Zeitz, Martin; Hamann, Alf; Klugewitz, Katja.

In: HEPATOLOGY, Vol. 48, No. 4, 10.2008, p. 1262-72.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schrage, A, Wechsung, K, Neumann, K, Schumann, M, Schulzke, J-D, Engelhardt, B, Zeitz, M, Hamann, A & Klugewitz, K 2008, 'Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines', HEPATOLOGY, vol. 48, no. 4, pp. 1262-72. https://doi.org/10.1002/hep.22443

APA

Schrage, A., Wechsung, K., Neumann, K., Schumann, M., Schulzke, J-D., Engelhardt, B., Zeitz, M., Hamann, A., & Klugewitz, K. (2008). Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines. HEPATOLOGY, 48(4), 1262-72. https://doi.org/10.1002/hep.22443

Vancouver

Schrage A, Wechsung K, Neumann K, Schumann M, Schulzke J-D, Engelhardt B et al. Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines. HEPATOLOGY. 2008 Oct;48(4):1262-72. https://doi.org/10.1002/hep.22443

Bibtex

@article{9b39cf7090c0449aaf599174f5c6574e,
title = "Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines",
abstract = "UNLABELLED: 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 (LSEC) inhibit or support the chemokine-driven transmigration and differentially influence the transmigration of pro-inflammatory or anti-inflammatory CD4(+) T cells, indicating a mechanism of hepatic immunoregulation. Finally, the results shed light on the molecular mechanisms by which LSEC modulate chemokine-dependent transmigration. LSEC significantly enhanced the chemotactic effect of CXC-motif chemokine ligand 12 (CXCL12) and CXCL9, but not of CXCL16 or CCL20, on naive and memory CD4(+) T cells of a T helper 1, T helper 2, or interleukin-10-producing phenotype. In contrast, brain and lymphatic endothelioma cells and ex vivo isolated lung endothelia inhibited chemokine-driven transmigration. As for the molecular mechanisms, chemokine-induced activation of LSEC was excluded by blockage of G(i)-protein-coupled signaling and the use of knockout mice. After preincubation of CXCL12 to the basal side, LSEC took up CXCL12 and enhanced transmigration as efficiently as in the presence of the soluble chemokine. Blockage of transcytosis in LSEC significantly inhibited this effect, and this suggested that chemokines taken up from the basolateral side and presented on the luminal side of endothelial cells trigger T cell transmigration.CONCLUSION: Our findings demonstrate a unique capacity of LSEC to present chemokines to circulating lymphocytes and highlight the importance of endothelial cells for the in vivo effects of chemokines. Chemokine presentation by LSEC could provide a future therapeutic target for inhibiting lymphocyte immigration and suppressing hepatic inflammation.",
keywords = "Animals, CD4-Positive T-Lymphocytes, Cell Line, Cell Movement, Cells, Cultured, Chemokine CXCL12, Chemokine CXCL9, Endothelium, Female, Liver, Lung, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Animal, Receptors, CXCR3, Spleen, Th1 Cells, Th2 Cells",
author = "Arnhild Schrage and Katja Wechsung and Katrin Neumann and Michael Schumann and J{\"o}rg-Dieter Schulzke and Britta Engelhardt and Martin Zeitz and Alf Hamann and Katja Klugewitz",
year = "2008",
month = oct,
doi = "10.1002/hep.22443",
language = "English",
volume = "48",
pages = "1262--72",
journal = "HEPATOLOGY",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

RIS

TY - JOUR

T1 - Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

AU - Schrage, Arnhild

AU - Wechsung, Katja

AU - Neumann, Katrin

AU - Schumann, Michael

AU - Schulzke, Jörg-Dieter

AU - Engelhardt, Britta

AU - Zeitz, Martin

AU - Hamann, Alf

AU - Klugewitz, Katja

PY - 2008/10

Y1 - 2008/10

N2 - UNLABELLED: 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 (LSEC) inhibit or support the chemokine-driven transmigration and differentially influence the transmigration of pro-inflammatory or anti-inflammatory CD4(+) T cells, indicating a mechanism of hepatic immunoregulation. Finally, the results shed light on the molecular mechanisms by which LSEC modulate chemokine-dependent transmigration. LSEC significantly enhanced the chemotactic effect of CXC-motif chemokine ligand 12 (CXCL12) and CXCL9, but not of CXCL16 or CCL20, on naive and memory CD4(+) T cells of a T helper 1, T helper 2, or interleukin-10-producing phenotype. In contrast, brain and lymphatic endothelioma cells and ex vivo isolated lung endothelia inhibited chemokine-driven transmigration. As for the molecular mechanisms, chemokine-induced activation of LSEC was excluded by blockage of G(i)-protein-coupled signaling and the use of knockout mice. After preincubation of CXCL12 to the basal side, LSEC took up CXCL12 and enhanced transmigration as efficiently as in the presence of the soluble chemokine. Blockage of transcytosis in LSEC significantly inhibited this effect, and this suggested that chemokines taken up from the basolateral side and presented on the luminal side of endothelial cells trigger T cell transmigration.CONCLUSION: Our findings demonstrate a unique capacity of LSEC to present chemokines to circulating lymphocytes and highlight the importance of endothelial cells for the in vivo effects of chemokines. Chemokine presentation by LSEC could provide a future therapeutic target for inhibiting lymphocyte immigration and suppressing hepatic inflammation.

AB - UNLABELLED: 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 (LSEC) inhibit or support the chemokine-driven transmigration and differentially influence the transmigration of pro-inflammatory or anti-inflammatory CD4(+) T cells, indicating a mechanism of hepatic immunoregulation. Finally, the results shed light on the molecular mechanisms by which LSEC modulate chemokine-dependent transmigration. LSEC significantly enhanced the chemotactic effect of CXC-motif chemokine ligand 12 (CXCL12) and CXCL9, but not of CXCL16 or CCL20, on naive and memory CD4(+) T cells of a T helper 1, T helper 2, or interleukin-10-producing phenotype. In contrast, brain and lymphatic endothelioma cells and ex vivo isolated lung endothelia inhibited chemokine-driven transmigration. As for the molecular mechanisms, chemokine-induced activation of LSEC was excluded by blockage of G(i)-protein-coupled signaling and the use of knockout mice. After preincubation of CXCL12 to the basal side, LSEC took up CXCL12 and enhanced transmigration as efficiently as in the presence of the soluble chemokine. Blockage of transcytosis in LSEC significantly inhibited this effect, and this suggested that chemokines taken up from the basolateral side and presented on the luminal side of endothelial cells trigger T cell transmigration.CONCLUSION: Our findings demonstrate a unique capacity of LSEC to present chemokines to circulating lymphocytes and highlight the importance of endothelial cells for the in vivo effects of chemokines. Chemokine presentation by LSEC could provide a future therapeutic target for inhibiting lymphocyte immigration and suppressing hepatic inflammation.

KW - Animals

KW - CD4-Positive T-Lymphocytes

KW - Cell Line

KW - Cell Movement

KW - Cells, Cultured

KW - Chemokine CXCL12

KW - Chemokine CXCL9

KW - Endothelium

KW - Female

KW - Liver

KW - Lung

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Models, Animal

KW - Receptors, CXCR3

KW - Spleen

KW - Th1 Cells

KW - Th2 Cells

U2 - 10.1002/hep.22443

DO - 10.1002/hep.22443

M3 - SCORING: Journal article

C2 - 18697212

VL - 48

SP - 1262

EP - 1272

JO - HEPATOLOGY

JF - HEPATOLOGY

SN - 0270-9139

IS - 4

ER -