Cell-autonomous regulation of neutrophil migration by the D6 chemokine decoy receptor

Rot, A., McKimmie, C., Burt, C.L., Pallas, K.J., Jamieson, T., Pruenster, M., Horuk, R., Nibbs, R.J.B. and Graham, G.J. (2013) Cell-autonomous regulation of neutrophil migration by the D6 chemokine decoy receptor. Journal of Immunology, 190(12), pp. 6450-6456. (doi: 10.4049/jimmunol.1201429)

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Abstract

Chemokines, acting on their cognate receptors on infiltrating leukocytes, drive the inflammatory response. We have been interested in determining roles and potential mechanisms for the atypical chemokine-scavenging receptor D6 in the regulation of inflammation. In this study, we show that a psoriasis-like pathology that arises in inflamed skins of D6-deficient mice is characterized by a massive and aberrant localization of neutrophils to the dermal/epidermal junction, which is associated with development of the pathology. Such misplacement of neutrophils is also seen with D6-deficient mice in other inflammatory models, suggesting a role for D6 in the spatial positioning of neutrophils within inflamed sites. We further show that D6 functions cell autonomously in this context and that D6, expressed by neutrophils, limits their migrational responses to CCR1 ligands such as CCL3. Our data therefore indicate that D6 is able to play a cell-autonomous role as a migratory rheostat restricting migration of D6-expressing cells such as neutrophils toward ligands for coexpressed inflammatory chemokine receptors. These data have important implications for our understanding of the roles for D6 in regulating inflammation and for our understanding of the control of spatial positioning of leukocytes at inflamed sites.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Pallas, Mr Kenny and Nibbs, Professor Rob and Jamieson, Mr Thomas and McKimmie, Dr Clive and Graham, Professor Gerard
Authors: Rot, A., McKimmie, C., Burt, C.L., Pallas, K.J., Jamieson, T., Pruenster, M., Horuk, R., Nibbs, R.J.B., and Graham, G.J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Journal of Immunology
Journal Abbr.:J. Immunol.
ISSN:0022-1767
ISSN (Online):1550-6606

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