Elevated ACKR2 expression is a common feature of inflammatory arthropathies

Baldwin, H. M., Singh, M. D., Codullo, V., King, V., Wilson, H., McInnes, I. and Graham, G. J. (2017) Elevated ACKR2 expression is a common feature of inflammatory arthropathies. Rheumatology, 56(9), pp. 1607-1617. (doi:10.1093/rheumatology/kex176) (PMID:28486662) (PMCID:PMC5850605)

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Abstract

Objectives. Chemokines are essential contributors to leucocyte accumulation at sites of inflammatory pathology. Interfering with chemokine or chemokine receptor function therefore represents a plausible therapeutic option. However, our currently limited understanding of chemokine orchestration of inflammatory responses means that such therapies have not yet been fully developed. We have a particular interest in the family of atypical chemokine receptors that fine-tune, or resolve, chemokine-driven responses. In particular we are interested in atypical chemokine receptor 2 (ACKR2), which is a scavenging receptor for inflammatory CC-chemokines and that therefore helps to resolve in vivo inflammatory responses. The objective of the current study was to examine ACKR2 expression in common arthropathies. Methods. ACKR2 expression was measured by a combination of qPCR and immuno-histochemistry. In addition, circulating cytokine and chemokine levels in patient plasma were assessed using multiplexing approaches. Results. Expression of ACKR2 was elevated on peripheral blood cells as well as on leucocytes and stromal cells in synovial tissue. Expression on peripheral blood leucocytes correlated with, and could be regulated by, circulating cytokines with particularly strong associations being seen with IL-6 and hepatocyte growth factor. In addition, expression within the synovium was coincident with aggregates of lymphocytes, potentially atopic follicles and sites of high inflammatory chemokine expression. Similarly increased levels of ACKR2 have been reported in psoriasis and SSc. Conclusion. Our data clearly show increased ACKR2 in a variety of arthropathies and taking into account our, and others’, previous data we now propose that elevated ACKR2 expression is a common feature of inflammatory pathologies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Wilson, Dr Hilary and King, Dr Vicky and Singh, Mr Mark and Baldwin, Dr Helen and Graham, Professor Gerard
Authors: Baldwin, H. M., Singh, M. D., Codullo, V., King, V., Wilson, H., McInnes, I., and Graham, G. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Rheumatology
Publisher:Oxford University Press
ISSN:1462-0324
ISSN (Online):1462-0332
Published Online:09 May 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Rheumatology 56(9): 1607-1617
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
600961Dissecting the chemokine basis for the orchestration of the in vivo inflammatory responseGerard GrahamWellcome Trust (WELLCOTR)099251/Z/12/ZIII -IMMUNOLOGY
681091The ACKR2-CCR2 axis in development and diseaseGerard GrahamMedical Research Council (MRC)MR/M019764/1III -IMMUNOLOGY