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Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion

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Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion. / Höchst, Bastian; Schildberg, Frank A; Sauerborn, Pia; Gäbel, Yvonne A; Gevensleben, Heidrun; Goltz, Diane; Heukamp, Lukas C; Türler, Andreas; Ballmaier, Matthias; Gieseke, Friederike; Müller, Ingo; Kalff, Jörg; Kurts, Christian; Knolle, Percy A; Diehl, Linda.

In: J HEPATOL, Vol. 59, No. 3, 01.09.2013, p. 528-35.

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

Harvard

Höchst, B, Schildberg, FA, Sauerborn, P, Gäbel, YA, Gevensleben, H, Goltz, D, Heukamp, LC, Türler, A, Ballmaier, M, Gieseke, F, Müller, I, Kalff, J, Kurts, C, Knolle, PA & Diehl, L 2013, 'Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion', J HEPATOL, vol. 59, no. 3, pp. 528-35. https://doi.org/10.1016/j.jhep.2013.04.033

APA

Höchst, B., Schildberg, F. A., Sauerborn, P., Gäbel, Y. A., Gevensleben, H., Goltz, D., Heukamp, L. C., Türler, A., Ballmaier, M., Gieseke, F., Müller, I., Kalff, J., Kurts, C., Knolle, P. A., & Diehl, L. (2013). Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion. J HEPATOL, 59(3), 528-35. https://doi.org/10.1016/j.jhep.2013.04.033

Vancouver

Höchst B, Schildberg FA, Sauerborn P, Gäbel YA, Gevensleben H, Goltz D et al. Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion. J HEPATOL. 2013 Sep 1;59(3):528-35. https://doi.org/10.1016/j.jhep.2013.04.033

Bibtex

@article{6605114b9ab7401aa63ea89ea1732faa,
title = "Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion",
abstract = "BACKGROUND & AIMS: Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of cells associated with the suppression of immunity. However, little is known about how or where MDSCs are induced and from which cells they originate. The liver is known for its immune regulatory functions. Here, we investigated the capacity of human hepatic stellate cells (HSCs) to transform peripheral blood monocytes into MDSCs.METHODS: We cultured freshly isolated human monocytes from healthy donors on primary human HSCs or an HSC cell-line and characterized the phenotype and function of resulting CD14(+)HLA-DR(-/low) monocytes by flow cytometry, quantitative PCR, and functional assays. We analyzed the molecular mechanisms underlying the induction and function of the CD14(+)HLA-DR(-/low) cells by using blocking antibodies or knock-down technology.RESULTS: Mature peripheral blood monocytes co-cultured with HSCs downregulated HLA-DR and developed a phenotypic and functional profile similar to MDSCs. Only activated but not freshly isolated HSCs were capable of inducing CD14(+)HLA-DR(-/low) cells. Such CD14(+)HLA-DR(-/low) monocyte-derived MDSCs suppressed T-cell proliferation in an arginase-1 dependent fashion. HSC-induced development of CD14(+)HLA-DR(-/low) monocyte-derived MDSCs was not mediated by soluble factors, but required physical interaction and was abrogated by blocking CD44.CONCLUSIONS: Our study shows that activated human HSCs convert mature peripheral blood monocytes into MDSCs. As HSCs are activated during chronic inflammation, the subsequent local induction of MDSCs may prevent ensuing excessive liver injury. HSC-induced MDSCs functionally and phenotypically resemble those isolated from liver cancer patients. Thus, our data suggest that local generation of MDSCs by liver-resident HSCs may contribute to immune suppression during inflammation and cancer in the liver.",
keywords = "Antigens, CD14, Antigens, CD44, Arginase, Cell Communication, Cell Differentiation, Cell Line, Cell Proliferation, Coculture Techniques, Down-Regulation, HLA-DR Antigens, Hepatic Stellate Cells, Humans, Immune Tolerance, Lymphocyte Activation, Monocytes, Myeloid Cells, T-Lymphocytes",
author = "Bastian H{\"o}chst and Schildberg, {Frank A} and Pia Sauerborn and G{\"a}bel, {Yvonne A} and Heidrun Gevensleben and Diane Goltz and Heukamp, {Lukas C} and Andreas T{\"u}rler and Matthias Ballmaier and Friederike Gieseke and Ingo M{\"u}ller and J{\"o}rg Kalff and Christian Kurts and Knolle, {Percy A} and Linda Diehl",
note = "Copyright {\textcopyright} 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2013",
month = sep,
day = "1",
doi = "10.1016/j.jhep.2013.04.033",
language = "English",
volume = "59",
pages = "528--35",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion

AU - Höchst, Bastian

AU - Schildberg, Frank A

AU - Sauerborn, Pia

AU - Gäbel, Yvonne A

AU - Gevensleben, Heidrun

AU - Goltz, Diane

AU - Heukamp, Lukas C

AU - Türler, Andreas

AU - Ballmaier, Matthias

AU - Gieseke, Friederike

AU - Müller, Ingo

AU - Kalff, Jörg

AU - Kurts, Christian

AU - Knolle, Percy A

AU - Diehl, Linda

N1 - Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2013/9/1

Y1 - 2013/9/1

N2 - BACKGROUND & AIMS: Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of cells associated with the suppression of immunity. However, little is known about how or where MDSCs are induced and from which cells they originate. The liver is known for its immune regulatory functions. Here, we investigated the capacity of human hepatic stellate cells (HSCs) to transform peripheral blood monocytes into MDSCs.METHODS: We cultured freshly isolated human monocytes from healthy donors on primary human HSCs or an HSC cell-line and characterized the phenotype and function of resulting CD14(+)HLA-DR(-/low) monocytes by flow cytometry, quantitative PCR, and functional assays. We analyzed the molecular mechanisms underlying the induction and function of the CD14(+)HLA-DR(-/low) cells by using blocking antibodies or knock-down technology.RESULTS: Mature peripheral blood monocytes co-cultured with HSCs downregulated HLA-DR and developed a phenotypic and functional profile similar to MDSCs. Only activated but not freshly isolated HSCs were capable of inducing CD14(+)HLA-DR(-/low) cells. Such CD14(+)HLA-DR(-/low) monocyte-derived MDSCs suppressed T-cell proliferation in an arginase-1 dependent fashion. HSC-induced development of CD14(+)HLA-DR(-/low) monocyte-derived MDSCs was not mediated by soluble factors, but required physical interaction and was abrogated by blocking CD44.CONCLUSIONS: Our study shows that activated human HSCs convert mature peripheral blood monocytes into MDSCs. As HSCs are activated during chronic inflammation, the subsequent local induction of MDSCs may prevent ensuing excessive liver injury. HSC-induced MDSCs functionally and phenotypically resemble those isolated from liver cancer patients. Thus, our data suggest that local generation of MDSCs by liver-resident HSCs may contribute to immune suppression during inflammation and cancer in the liver.

AB - BACKGROUND & AIMS: Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of cells associated with the suppression of immunity. However, little is known about how or where MDSCs are induced and from which cells they originate. The liver is known for its immune regulatory functions. Here, we investigated the capacity of human hepatic stellate cells (HSCs) to transform peripheral blood monocytes into MDSCs.METHODS: We cultured freshly isolated human monocytes from healthy donors on primary human HSCs or an HSC cell-line and characterized the phenotype and function of resulting CD14(+)HLA-DR(-/low) monocytes by flow cytometry, quantitative PCR, and functional assays. We analyzed the molecular mechanisms underlying the induction and function of the CD14(+)HLA-DR(-/low) cells by using blocking antibodies or knock-down technology.RESULTS: Mature peripheral blood monocytes co-cultured with HSCs downregulated HLA-DR and developed a phenotypic and functional profile similar to MDSCs. Only activated but not freshly isolated HSCs were capable of inducing CD14(+)HLA-DR(-/low) cells. Such CD14(+)HLA-DR(-/low) monocyte-derived MDSCs suppressed T-cell proliferation in an arginase-1 dependent fashion. HSC-induced development of CD14(+)HLA-DR(-/low) monocyte-derived MDSCs was not mediated by soluble factors, but required physical interaction and was abrogated by blocking CD44.CONCLUSIONS: Our study shows that activated human HSCs convert mature peripheral blood monocytes into MDSCs. As HSCs are activated during chronic inflammation, the subsequent local induction of MDSCs may prevent ensuing excessive liver injury. HSC-induced MDSCs functionally and phenotypically resemble those isolated from liver cancer patients. Thus, our data suggest that local generation of MDSCs by liver-resident HSCs may contribute to immune suppression during inflammation and cancer in the liver.

KW - Antigens, CD14

KW - Antigens, CD44

KW - Arginase

KW - Cell Communication

KW - Cell Differentiation

KW - Cell Line

KW - Cell Proliferation

KW - Coculture Techniques

KW - Down-Regulation

KW - HLA-DR Antigens

KW - Hepatic Stellate Cells

KW - Humans

KW - Immune Tolerance

KW - Lymphocyte Activation

KW - Monocytes

KW - Myeloid Cells

KW - T-Lymphocytes

U2 - 10.1016/j.jhep.2013.04.033

DO - 10.1016/j.jhep.2013.04.033

M3 - SCORING: Journal article

C2 - 23665041

VL - 59

SP - 528

EP - 535

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 3

ER -