Cargando…
Spread of Psoriasiform Inflammation to Remote Tissues Is Restricted by the Atypical Chemokine Receptor ACKR2
Elucidating the poorly defined mechanisms by which inflammatory lesions are spatially restricted in vivo is of critical importance in understanding skin disease. Chemokines are the principal regulators of leukocyte migration and are essential in the initiation and maintenance of inflammation. The me...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5176004/ https://www.ncbi.nlm.nih.gov/pubmed/27568525 http://dx.doi.org/10.1016/j.jid.2016.07.039 |
_version_ | 1782484753832738816 |
---|---|
author | Shams, Kave Wilson, Gillian J. Singh, Mark van den Bogaard, Ellen H. Le Brocq, Michelle L. Holmes, Susan Schalkwijk, Joost Burden, A. David McKimmie, Clive S. Graham, Gerard J. |
author_facet | Shams, Kave Wilson, Gillian J. Singh, Mark van den Bogaard, Ellen H. Le Brocq, Michelle L. Holmes, Susan Schalkwijk, Joost Burden, A. David McKimmie, Clive S. Graham, Gerard J. |
author_sort | Shams, Kave |
collection | PubMed |
description | Elucidating the poorly defined mechanisms by which inflammatory lesions are spatially restricted in vivo is of critical importance in understanding skin disease. Chemokines are the principal regulators of leukocyte migration and are essential in the initiation and maintenance of inflammation. The membrane-bound psoriasis-associated atypical chemokine receptor 2 (ACKR2) binds, internalizes and degrades most proinflammatory CC-chemokines. Here we investigate the role of ACKR2 in limiting the spread of cutaneous psoriasiform inflammation to sites that are remote from the primary lesion. Circulating factors capable of regulating ACKR2 function at remote sites were identified and examined using a combination of clinical samples, relevant primary human cell cultures, in vitro migration assays, and the imiquimod-induced model of psoriasiform skin inflammation. Localized inflammation and IFN-γ together up-regulate ACKR2 in remote tissues, protecting them from the spread of inflammation. ACKR2 controls inflammatory T-cell chemotaxis and positioning within the skin, preventing an epidermal influx that is associated with lesion development. Our results have important implications for our understanding of how spatial restriction is imposed on the spread of inflammatory lesions and highlight systemic ACKR2 induction as a therapeutic strategy in the treatment and prevention of psoriasis and potentially a broad range of other immune-mediated diseases. |
format | Online Article Text |
id | pubmed-5176004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-51760042017-01-01 Spread of Psoriasiform Inflammation to Remote Tissues Is Restricted by the Atypical Chemokine Receptor ACKR2 Shams, Kave Wilson, Gillian J. Singh, Mark van den Bogaard, Ellen H. Le Brocq, Michelle L. Holmes, Susan Schalkwijk, Joost Burden, A. David McKimmie, Clive S. Graham, Gerard J. J Invest Dermatol Original Article Elucidating the poorly defined mechanisms by which inflammatory lesions are spatially restricted in vivo is of critical importance in understanding skin disease. Chemokines are the principal regulators of leukocyte migration and are essential in the initiation and maintenance of inflammation. The membrane-bound psoriasis-associated atypical chemokine receptor 2 (ACKR2) binds, internalizes and degrades most proinflammatory CC-chemokines. Here we investigate the role of ACKR2 in limiting the spread of cutaneous psoriasiform inflammation to sites that are remote from the primary lesion. Circulating factors capable of regulating ACKR2 function at remote sites were identified and examined using a combination of clinical samples, relevant primary human cell cultures, in vitro migration assays, and the imiquimod-induced model of psoriasiform skin inflammation. Localized inflammation and IFN-γ together up-regulate ACKR2 in remote tissues, protecting them from the spread of inflammation. ACKR2 controls inflammatory T-cell chemotaxis and positioning within the skin, preventing an epidermal influx that is associated with lesion development. Our results have important implications for our understanding of how spatial restriction is imposed on the spread of inflammatory lesions and highlight systemic ACKR2 induction as a therapeutic strategy in the treatment and prevention of psoriasis and potentially a broad range of other immune-mediated diseases. Elsevier 2017-01 /pmc/articles/PMC5176004/ /pubmed/27568525 http://dx.doi.org/10.1016/j.jid.2016.07.039 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Article Shams, Kave Wilson, Gillian J. Singh, Mark van den Bogaard, Ellen H. Le Brocq, Michelle L. Holmes, Susan Schalkwijk, Joost Burden, A. David McKimmie, Clive S. Graham, Gerard J. Spread of Psoriasiform Inflammation to Remote Tissues Is Restricted by the Atypical Chemokine Receptor ACKR2 |
title | Spread of Psoriasiform Inflammation to Remote Tissues Is Restricted by the Atypical Chemokine Receptor ACKR2 |
title_full | Spread of Psoriasiform Inflammation to Remote Tissues Is Restricted by the Atypical Chemokine Receptor ACKR2 |
title_fullStr | Spread of Psoriasiform Inflammation to Remote Tissues Is Restricted by the Atypical Chemokine Receptor ACKR2 |
title_full_unstemmed | Spread of Psoriasiform Inflammation to Remote Tissues Is Restricted by the Atypical Chemokine Receptor ACKR2 |
title_short | Spread of Psoriasiform Inflammation to Remote Tissues Is Restricted by the Atypical Chemokine Receptor ACKR2 |
title_sort | spread of psoriasiform inflammation to remote tissues is restricted by the atypical chemokine receptor ackr2 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5176004/ https://www.ncbi.nlm.nih.gov/pubmed/27568525 http://dx.doi.org/10.1016/j.jid.2016.07.039 |
work_keys_str_mv | AT shamskave spreadofpsoriasiforminflammationtoremotetissuesisrestrictedbytheatypicalchemokinereceptorackr2 AT wilsongillianj spreadofpsoriasiforminflammationtoremotetissuesisrestrictedbytheatypicalchemokinereceptorackr2 AT singhmark spreadofpsoriasiforminflammationtoremotetissuesisrestrictedbytheatypicalchemokinereceptorackr2 AT vandenbogaardellenh spreadofpsoriasiforminflammationtoremotetissuesisrestrictedbytheatypicalchemokinereceptorackr2 AT lebrocqmichellel spreadofpsoriasiforminflammationtoremotetissuesisrestrictedbytheatypicalchemokinereceptorackr2 AT holmessusan spreadofpsoriasiforminflammationtoremotetissuesisrestrictedbytheatypicalchemokinereceptorackr2 AT schalkwijkjoost spreadofpsoriasiforminflammationtoremotetissuesisrestrictedbytheatypicalchemokinereceptorackr2 AT burdenadavid spreadofpsoriasiforminflammationtoremotetissuesisrestrictedbytheatypicalchemokinereceptorackr2 AT mckimmieclives spreadofpsoriasiforminflammationtoremotetissuesisrestrictedbytheatypicalchemokinereceptorackr2 AT grahamgerardj spreadofpsoriasiforminflammationtoremotetissuesisrestrictedbytheatypicalchemokinereceptorackr2 |