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The chemokine receptor D6 limits the inflammatory response in vivo

Nature Immunology volume 6, pages 403–411 (2005)Cite this article

Abstract

How the inflammatory response is initiated has been well defined but relatively little is known about how such responses are resolved. Here we show that the D6 chemokine receptor is involved in the post-inflammatory clearance of β-chemokines from cutaneous sites. After induction of inflammation by phorbol esters, wild-type mice showed a transient inflammatory response. However, in D6-deficient mice, an excess concentration of residual chemokines caused a notable inflammatory pathology with similarities to human psoriasis. These results suggest that D6 is involved in the resolution of the cutaneous inflammatory response.

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Figure 1: The generation of D6-deficient mice.
Figure 2: The clearance of cutaneous β-chemokines is delayed in the D6-deficient mice.
Figure 3: Development of an inflammatory cutaneous pathology in D6-deficient mice.
Figure 4: Inflamed D6-deficient mouse skin is characterized by altered proliferation, differentiation, angiogenesis and MIP-2 production.
Figure 5: The cutaneous pathology that develops in the D6-deficient mice is dependent on TNF and chemokines.
Figure 6: Characterization of the cellular infiltrate in inflamed D6-deficient mouse skin.
Figure 7: The cutaneous pathology in the D6-deficient mice is T cell dependent.
Figure 8: Mast cell products are involved in the development of the cutaneous inflammatory pathology in the D6-deficient mice.

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Acknowledgements

The authors thank F.Y. Liew, P. Garside, A. Mowat and I. McInnes for discussions and for comments on the manuscript. Supported by Cancer Research UK.

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Author notes

  1. Thomas Jamieson and Donald N Cook: These authors contributed equally to this work.

Authors and Affiliations

  1. The Beatson Institute for Cancer Research, Glasgow, G61 1BD, UK

    Thomas Jamieson, Robert J B Nibbs & Gerard J Graham

  2. Department of Medicine, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, 27706, North Carolina, USA

    Donald N Cook

  3. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, G11 6NT, UK

    Robert J B Nibbs, Pauline Mclean & Gerard J Graham

  4. Novartis Institutes for Biomedical Research, Vienna, A1230, Austria

    Antal Rot

  5. Department of Veterinary Pathology, University of Glasgow, Glasgow, G61 1QH, UK

    Colin Nixon

  6. Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Universidad Autónoma, Cantoblanco, 28049, Madrid, Spain

    Antonio Alcami

  7. Immunobiology Center, Mount Sinai School of Medicine, New York, 10029, New York, USA

    Sergio A Lira

  8. Schering-Plough Research Institute, Kenilworth, 07033, New Jersey, USA

    Maria Wiekowski

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Jamieson, T., Cook, D., Nibbs, R. et al. The chemokine receptor D6 limits the inflammatory response in vivo. Nat Immunol 6, 403–411 (2005). https://doi.org/10.1038/ni1182

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