Hemopoietic cell expression of the chemokine decoy receptor D6 is dynamic and regulated by GATA1

Clive S. McKimmie; Alasdair R. Fraser; Chris Hansell; Laura Gutierrez; Sjaak Philipsen; Laura Connell; Antal Rot; Mariola Kurowska-Stolarska; Paz Carreno; Monika Pruenster; Chung-Ching Chu; Giovanna Lombardi; Christina Halsey; Lain B. McInnes; Foo Y. Liew; Robert J. Nibbs; Gerard J. Graham

Hemopoietic cell expression of the chemokine decoy receptor D6 is dynamic and regulated by GATA1

Clive S. McKimmie, Alasdair R. Fraser, Chris Hansell, Laura Gutierrez, Sjaak Philipsen, Laura Connell, Antal Rot, Mariola Kurowska-Stolarska, Paz Carreno, Monika Pruenster, Chung-Ching Chu, Giovanna Lombardi, Christina Halsey, Lain B. McInnes, Foo Y. Liew, Robert J. Nibbs, Gerard J. Graham

Research output: Contribution to journal › Article › peer-review

Abstract

D6 scavenges inflammatory chemokines and is essential for the regulation of inflammatory and immune responses. Mechanisms explaining the cellular basis for D6 function have been based on D6 expression by lymphatic endothelial cells. In this study, we demonstrate that functional D6 is also expressed by murine and human hemopoietic cells and that this expression can be regulated by pro- and anti-inflammatory agents. D6 expression was highest in B cells and dendritic cells (DCs). In myeloid cells, LPS down-regulated expression, while TGF-beta up-regulated expression. Activation of T cells with anti-CD3 and soluble CD28 up-regulated mRNA expression 20-fold, while maturation of human macrophage and megakaryocyte precursors also up-regulated D6 expression. Competition assays demonstrated that chemokine uptake was D6 dependent in human leukocytes, whereas mouse D6-null cells failed to uptake and clear inflammatory chemokines. Furthermore, we present evidence indicating that D6 expression is GATA1 dependent, thus explaining D6 expression in myeloid progenitor cells, mast cells, megakaryocytes, and DCs. We propose a model for D6 function in which leukocytes, within inflamed sites, activate D6 expression and thus trigger resolution of inflammatory responses. Our data on D6 expression by circulating DCs and B cells also suggest alternative roles for D6, perhaps in the coordination of innate and adaptive immune responses. These data therefore alter our models of in vivo D6 function and suggest possible discrete, and novel, roles for D6 on lymphatic endothelial cells and leukocytes.

Original language	English
Pages (from-to)	3353 - 3363
Number of pages	11
Journal	Journal of Immunology
Volume	181
Issue number	5
Publication status	Published - 2008

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McKimmie, C. S., Fraser, A. R., Hansell, C., Gutierrez, L., Philipsen, S., Connell, L., Rot, A., Kurowska-Stolarska, M., Carreno, P., Pruenster, M., Chu, C.-C., Lombardi, G., Halsey, C., McInnes, L. B., Liew, F. Y., Nibbs, R. J., & Graham, G. J. (2008). Hemopoietic cell expression of the chemokine decoy receptor D6 is dynamic and regulated by GATA1. Journal of Immunology, 181(5), 3353 - 3363.

@article{b372a395b8864d96863281a9b78d3b30,

title = "Hemopoietic cell expression of the chemokine decoy receptor D6 is dynamic and regulated by GATA1",

abstract = "D6 scavenges inflammatory chemokines and is essential for the regulation of inflammatory and immune responses. Mechanisms explaining the cellular basis for D6 function have been based on D6 expression by lymphatic endothelial cells. In this study, we demonstrate that functional D6 is also expressed by murine and human hemopoietic cells and that this expression can be regulated by pro- and anti-inflammatory agents. D6 expression was highest in B cells and dendritic cells (DCs). In myeloid cells, LPS down-regulated expression, while TGF-beta up-regulated expression. Activation of T cells with anti-CD3 and soluble CD28 up-regulated mRNA expression 20-fold, while maturation of human macrophage and megakaryocyte precursors also up-regulated D6 expression. Competition assays demonstrated that chemokine uptake was D6 dependent in human leukocytes, whereas mouse D6-null cells failed to uptake and clear inflammatory chemokines. Furthermore, we present evidence indicating that D6 expression is GATA1 dependent, thus explaining D6 expression in myeloid progenitor cells, mast cells, megakaryocytes, and DCs. We propose a model for D6 function in which leukocytes, within inflamed sites, activate D6 expression and thus trigger resolution of inflammatory responses. Our data on D6 expression by circulating DCs and B cells also suggest alternative roles for D6, perhaps in the coordination of innate and adaptive immune responses. These data therefore alter our models of in vivo D6 function and suggest possible discrete, and novel, roles for D6 on lymphatic endothelial cells and leukocytes.",

author = "McKimmie, {Clive S.} and Fraser, {Alasdair R.} and Chris Hansell and Laura Gutierrez and Sjaak Philipsen and Laura Connell and Antal Rot and Mariola Kurowska-Stolarska and Paz Carreno and Monika Pruenster and Chung-Ching Chu and Giovanna Lombardi and Christina Halsey and McInnes, {Lain B.} and Liew, {Foo Y.} and Nibbs, {Robert J.} and Graham, {Gerard J.}",

year = "2008",

language = "English",

volume = "181",

pages = "3353 -- 3363",

journal = "Journal of Immunology",

issn = "1550-6606",

publisher = "American Association of Immunologists",

number = "5",

}

McKimmie, CS, Fraser, AR, Hansell, C, Gutierrez, L, Philipsen, S, Connell, L, Rot, A, Kurowska-Stolarska, M, Carreno, P, Pruenster, M, Chu, C-C, Lombardi, G, Halsey, C, McInnes, LB, Liew, FY, Nibbs, RJ & Graham, GJ 2008, 'Hemopoietic cell expression of the chemokine decoy receptor D6 is dynamic and regulated by GATA1', Journal of Immunology, vol. 181, no. 5, pp. 3353 - 3363.

TY - JOUR

T1 - Hemopoietic cell expression of the chemokine decoy receptor D6 is dynamic and regulated by GATA1

AU - McKimmie, Clive S.

AU - Fraser, Alasdair R.

AU - Hansell, Chris

AU - Gutierrez, Laura

AU - Philipsen, Sjaak

AU - Connell, Laura

AU - Rot, Antal

AU - Kurowska-Stolarska, Mariola

AU - Carreno, Paz

AU - Pruenster, Monika

AU - Chu, Chung-Ching

AU - Lombardi, Giovanna

AU - Halsey, Christina

AU - McInnes, Lain B.

AU - Liew, Foo Y.

AU - Nibbs, Robert J.

AU - Graham, Gerard J.

PY - 2008

Y1 - 2008

N2 - D6 scavenges inflammatory chemokines and is essential for the regulation of inflammatory and immune responses. Mechanisms explaining the cellular basis for D6 function have been based on D6 expression by lymphatic endothelial cells. In this study, we demonstrate that functional D6 is also expressed by murine and human hemopoietic cells and that this expression can be regulated by pro- and anti-inflammatory agents. D6 expression was highest in B cells and dendritic cells (DCs). In myeloid cells, LPS down-regulated expression, while TGF-beta up-regulated expression. Activation of T cells with anti-CD3 and soluble CD28 up-regulated mRNA expression 20-fold, while maturation of human macrophage and megakaryocyte precursors also up-regulated D6 expression. Competition assays demonstrated that chemokine uptake was D6 dependent in human leukocytes, whereas mouse D6-null cells failed to uptake and clear inflammatory chemokines. Furthermore, we present evidence indicating that D6 expression is GATA1 dependent, thus explaining D6 expression in myeloid progenitor cells, mast cells, megakaryocytes, and DCs. We propose a model for D6 function in which leukocytes, within inflamed sites, activate D6 expression and thus trigger resolution of inflammatory responses. Our data on D6 expression by circulating DCs and B cells also suggest alternative roles for D6, perhaps in the coordination of innate and adaptive immune responses. These data therefore alter our models of in vivo D6 function and suggest possible discrete, and novel, roles for D6 on lymphatic endothelial cells and leukocytes.

AB - D6 scavenges inflammatory chemokines and is essential for the regulation of inflammatory and immune responses. Mechanisms explaining the cellular basis for D6 function have been based on D6 expression by lymphatic endothelial cells. In this study, we demonstrate that functional D6 is also expressed by murine and human hemopoietic cells and that this expression can be regulated by pro- and anti-inflammatory agents. D6 expression was highest in B cells and dendritic cells (DCs). In myeloid cells, LPS down-regulated expression, while TGF-beta up-regulated expression. Activation of T cells with anti-CD3 and soluble CD28 up-regulated mRNA expression 20-fold, while maturation of human macrophage and megakaryocyte precursors also up-regulated D6 expression. Competition assays demonstrated that chemokine uptake was D6 dependent in human leukocytes, whereas mouse D6-null cells failed to uptake and clear inflammatory chemokines. Furthermore, we present evidence indicating that D6 expression is GATA1 dependent, thus explaining D6 expression in myeloid progenitor cells, mast cells, megakaryocytes, and DCs. We propose a model for D6 function in which leukocytes, within inflamed sites, activate D6 expression and thus trigger resolution of inflammatory responses. Our data on D6 expression by circulating DCs and B cells also suggest alternative roles for D6, perhaps in the coordination of innate and adaptive immune responses. These data therefore alter our models of in vivo D6 function and suggest possible discrete, and novel, roles for D6 on lymphatic endothelial cells and leukocytes.

M3 - Article

SN - 1550-6606

VL - 181

SP - 3353

EP - 3363

JO - Journal of Immunology

JF - Journal of Immunology

IS - 5

ER -

Hemopoietic cell expression of the chemokine decoy receptor D6 is dynamic and regulated by GATA1

Abstract

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