Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis

Singh, M.D. et al. (2012) Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis. American Journal of Pathology, 181(4), pp. 1158-1164. (doi:10.1016/j.ajpath.2012.06.042) (PMID:22867710) (PMCID:PMC3532592)

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Abstract

D6 is a scavenging-receptor for inflammatory CC chemokines that are essential for resolution of inflammatory responses in mice. Here, we demonstrate that D6 plays a central role in controlling cutaneous inflammation, and that D6 deficiency is associated with development of a psoriasis-like pathology in response to varied inflammatory stimuli in mice. Examination of D6 expression in human psoriatic skin revealed markedly elevated expression in both the epidermis and lymphatic endothelium in "uninvolved" psoriatic skin (ie, skin that was more than 8 cm distant from psoriatic plaques). Notably, this increased D6 expression is associated with elevated inflammatory chemokine expression, but an absence of plaque development, in uninvolved skin. Along with our previous observations of the ability of epidermally expressed transgenic D6 to impair cutaneous inflammatory responses, our data support a role for elevated D6 levels in suppressing inflammatory chemokine action and lesion development in uninvolved psoriatic skin. D6 expression consistently dropped in perilesional and lesional skin, coincident with development of psoriatic plaques. D6 expression in uninvolved skin also was reduced after trauma, indicative of a role for trauma-mediated reduction in D6 expression in triggering lesion development. Importantly, D6 is also elevated in peripheral blood leukocytes in psoriatic patients, indicating that upregulation may be a general protective response to inflammation. Together our data demonstrate a novel role for D6 as a regulator of the transition from uninvolved to lesional skin in psoriasis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Shams, Dr Kave and Baldwin, Dr Helen and Burden, Professor David and King, Dr Vicky and Pallas, Mr Kenny and Singh, Mr Mark and Jamieson, Mr Thomas and Holmes, Dr Susan and Graham, Professor Gerard
Authors: Singh, M.D., King, V., Baldwin, H., Burden, D., Thorrat, A., Holmes, S., McInnes, I.B., Nicoll, R., Shams, K., Pallas, K., Jamieson, T., Lee, K.M., Carballido, J.M., Rot, A., and Graham, G.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:American Journal of Pathology
Publisher:American Society for Investigative Pathology
ISSN:0002-9440
Published Online:04 August 2012
Copyright Holders:Copyright © 2012 American Society for Investigative Pathology
First Published:First published in American Journal of Pathology 181(4):1158-1164
Publisher Policy:Reproduced under a Creative Commons License

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