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Elevated ACKR2 expression is a common feature of inflammatory arthropathies

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 in...

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Autores principales: Baldwin, Helen M., Singh, Mark D., Codullo, Veronica, King, Vicky, Wilson, Hilary, McInnes, Iain, Graham, Gerard J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850605/
https://www.ncbi.nlm.nih.gov/pubmed/28486662
http://dx.doi.org/10.1093/rheumatology/kex176
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author Baldwin, Helen M.
Singh, Mark D.
Codullo, Veronica
King, Vicky
Wilson, Hilary
McInnes, Iain
Graham, Gerard J.
author_facet Baldwin, Helen M.
Singh, Mark D.
Codullo, Veronica
King, Vicky
Wilson, Hilary
McInnes, Iain
Graham, Gerard J.
author_sort Baldwin, Helen M.
collection PubMed
description 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.
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spelling pubmed-58506052018-03-23 Elevated ACKR2 expression is a common feature of inflammatory arthropathies Baldwin, Helen M. Singh, Mark D. Codullo, Veronica King, Vicky Wilson, Hilary McInnes, Iain Graham, Gerard J. Rheumatology (Oxford) Basic and Translational Science 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. Oxford University Press 2017-09 2017-05-09 /pmc/articles/PMC5850605/ /pubmed/28486662 http://dx.doi.org/10.1093/rheumatology/kex176 Text en © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic and Translational Science
Baldwin, Helen M.
Singh, Mark D.
Codullo, Veronica
King, Vicky
Wilson, Hilary
McInnes, Iain
Graham, Gerard J.
Elevated ACKR2 expression is a common feature of inflammatory arthropathies
title Elevated ACKR2 expression is a common feature of inflammatory arthropathies
title_full Elevated ACKR2 expression is a common feature of inflammatory arthropathies
title_fullStr Elevated ACKR2 expression is a common feature of inflammatory arthropathies
title_full_unstemmed Elevated ACKR2 expression is a common feature of inflammatory arthropathies
title_short Elevated ACKR2 expression is a common feature of inflammatory arthropathies
title_sort elevated ackr2 expression is a common feature of inflammatory arthropathies
topic Basic and Translational Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850605/
https://www.ncbi.nlm.nih.gov/pubmed/28486662
http://dx.doi.org/10.1093/rheumatology/kex176
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