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TGF-β-dependent induction of CD4⁺CD25⁺Foxp3⁺ Tregs by liver sinusoidal endothelial cells

Standard

TGF-β-dependent induction of CD4⁺CD25⁺Foxp3⁺ Tregs by liver sinusoidal endothelial cells. / Carambia, Antonella; Freund, Barbara; Schwinge, Dorothee; Heine, Markus; Laschtowitz, Alena; Huber, Samuel; Wraith, David C; Korn, Thomas; Schramm, Christoph; Lohse, Ansgar W; Heeren, Joerg; Herkel, Johannes.

In: J HEPATOL, Vol. 61, No. 3, 01.09.2014, p. 594-9.

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

Harvard

Carambia, A, Freund, B, Schwinge, D, Heine, M, Laschtowitz, A, Huber, S, Wraith, DC, Korn, T, Schramm, C, Lohse, AW, Heeren, J & Herkel, J 2014, 'TGF-β-dependent induction of CD4⁺CD25⁺Foxp3⁺ Tregs by liver sinusoidal endothelial cells', J HEPATOL, vol. 61, no. 3, pp. 594-9. https://doi.org/10.1016/j.jhep.2014.04.027

APA

Carambia, A., Freund, B., Schwinge, D., Heine, M., Laschtowitz, A., Huber, S., Wraith, D. C., Korn, T., Schramm, C., Lohse, A. W., Heeren, J., & Herkel, J. (2014). TGF-β-dependent induction of CD4⁺CD25⁺Foxp3⁺ Tregs by liver sinusoidal endothelial cells. J HEPATOL, 61(3), 594-9. https://doi.org/10.1016/j.jhep.2014.04.027

Vancouver

Carambia A, Freund B, Schwinge D, Heine M, Laschtowitz A, Huber S et al. TGF-β-dependent induction of CD4⁺CD25⁺Foxp3⁺ Tregs by liver sinusoidal endothelial cells. J HEPATOL. 2014 Sep 1;61(3):594-9. https://doi.org/10.1016/j.jhep.2014.04.027

Bibtex

@article{132f4d530d8b4ad499ce4e3510b8af94,
title = "TGF-β-dependent induction of CD4⁺CD25⁺Foxp3⁺ Tregs by liver sinusoidal endothelial cells",
abstract = "BACKGROUND & AIMS: CD4(+) CD25(+) Foxp3(+) regulatory T cells (Tregs) have a profound ability to control immune responses. We have previously shown that the liver is a major source of peripherally induced Tregs. Here, we investigate the liver cell types and molecular mechanisms responsible for hepatic Treg induction.METHODS: To assess the Treg-inducing potential of liver resident antigen-presenting cell types, we studied the conversion of Foxp3(-) non-Tregs into Foxp3(+) Tregs induced by liver dendritic cells (DCs), liver sinusoidal endothelial cells (LSECs), or Kupffer cells (KCs). The dependency of Treg induction on TGF-β was tested in Treg conversion assays using T cells with reduced TGF-β sensitivity. The suppressive potential of liver cell-induced Tregs was assessed by an in vitro suppression assay and in vivo, in the model of experimental autoimmune encephalomyelitis (EAE).RESULTS: All tested liver cell types were capable of inducing Foxp3(+) Tregs; however, LSECs were most efficient in inducing Tregs. Treg-induction was antigen-specific and depended on TGF-β. LSECs featured membrane-bound LAP/TGF-β and the anchor molecule GARP, which is required for tethering LAP/TGF-β to the cell membrane. LSEC-induced Tregs suppressed proliferation and cytokine secretion of effector T cells in vitro. LSEC-induced Tregs were also functional suppressors in vivo, as neuroantigen-specific Tregs induced by LSECs were able to suppress EAE.CONCLUSIONS: We demonstrate that LSECs are the major liver cell type responsible for TGF-β dependent hepatic Treg induction. The extraordinary capacity of LSECs to induce Tregs was associated with their unique ability to tether TGF-β to their membrane.",
author = "Antonella Carambia and Barbara Freund and Dorothee Schwinge and Markus Heine and Alena Laschtowitz and Samuel Huber and Wraith, {David C} and Thomas Korn and Christoph Schramm and Lohse, {Ansgar W} and Joerg Heeren and Johannes Herkel",
note = "Copyright {\textcopyright} 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2014",
month = sep,
day = "1",
doi = "10.1016/j.jhep.2014.04.027",
language = "English",
volume = "61",
pages = "594--9",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - TGF-β-dependent induction of CD4⁺CD25⁺Foxp3⁺ Tregs by liver sinusoidal endothelial cells

AU - Carambia, Antonella

AU - Freund, Barbara

AU - Schwinge, Dorothee

AU - Heine, Markus

AU - Laschtowitz, Alena

AU - Huber, Samuel

AU - Wraith, David C

AU - Korn, Thomas

AU - Schramm, Christoph

AU - Lohse, Ansgar W

AU - Heeren, Joerg

AU - Herkel, Johannes

N1 - Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - BACKGROUND & AIMS: CD4(+) CD25(+) Foxp3(+) regulatory T cells (Tregs) have a profound ability to control immune responses. We have previously shown that the liver is a major source of peripherally induced Tregs. Here, we investigate the liver cell types and molecular mechanisms responsible for hepatic Treg induction.METHODS: To assess the Treg-inducing potential of liver resident antigen-presenting cell types, we studied the conversion of Foxp3(-) non-Tregs into Foxp3(+) Tregs induced by liver dendritic cells (DCs), liver sinusoidal endothelial cells (LSECs), or Kupffer cells (KCs). The dependency of Treg induction on TGF-β was tested in Treg conversion assays using T cells with reduced TGF-β sensitivity. The suppressive potential of liver cell-induced Tregs was assessed by an in vitro suppression assay and in vivo, in the model of experimental autoimmune encephalomyelitis (EAE).RESULTS: All tested liver cell types were capable of inducing Foxp3(+) Tregs; however, LSECs were most efficient in inducing Tregs. Treg-induction was antigen-specific and depended on TGF-β. LSECs featured membrane-bound LAP/TGF-β and the anchor molecule GARP, which is required for tethering LAP/TGF-β to the cell membrane. LSEC-induced Tregs suppressed proliferation and cytokine secretion of effector T cells in vitro. LSEC-induced Tregs were also functional suppressors in vivo, as neuroantigen-specific Tregs induced by LSECs were able to suppress EAE.CONCLUSIONS: We demonstrate that LSECs are the major liver cell type responsible for TGF-β dependent hepatic Treg induction. The extraordinary capacity of LSECs to induce Tregs was associated with their unique ability to tether TGF-β to their membrane.

AB - BACKGROUND & AIMS: CD4(+) CD25(+) Foxp3(+) regulatory T cells (Tregs) have a profound ability to control immune responses. We have previously shown that the liver is a major source of peripherally induced Tregs. Here, we investigate the liver cell types and molecular mechanisms responsible for hepatic Treg induction.METHODS: To assess the Treg-inducing potential of liver resident antigen-presenting cell types, we studied the conversion of Foxp3(-) non-Tregs into Foxp3(+) Tregs induced by liver dendritic cells (DCs), liver sinusoidal endothelial cells (LSECs), or Kupffer cells (KCs). The dependency of Treg induction on TGF-β was tested in Treg conversion assays using T cells with reduced TGF-β sensitivity. The suppressive potential of liver cell-induced Tregs was assessed by an in vitro suppression assay and in vivo, in the model of experimental autoimmune encephalomyelitis (EAE).RESULTS: All tested liver cell types were capable of inducing Foxp3(+) Tregs; however, LSECs were most efficient in inducing Tregs. Treg-induction was antigen-specific and depended on TGF-β. LSECs featured membrane-bound LAP/TGF-β and the anchor molecule GARP, which is required for tethering LAP/TGF-β to the cell membrane. LSEC-induced Tregs suppressed proliferation and cytokine secretion of effector T cells in vitro. LSEC-induced Tregs were also functional suppressors in vivo, as neuroantigen-specific Tregs induced by LSECs were able to suppress EAE.CONCLUSIONS: We demonstrate that LSECs are the major liver cell type responsible for TGF-β dependent hepatic Treg induction. The extraordinary capacity of LSECs to induce Tregs was associated with their unique ability to tether TGF-β to their membrane.

U2 - 10.1016/j.jhep.2014.04.027

DO - 10.1016/j.jhep.2014.04.027

M3 - SCORING: Journal article

C2 - 24798620

VL - 61

SP - 594

EP - 599

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 3

ER -