Cargando…
ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity
The extracellular matrix (ECM) provides physical scaffolding for cellular constituents and initiates biochemical and biomechanical cues that are required for physiological activity of living tissues. The ECM enzyme ADAMTS5, a member of the ADAMTS (A Disintegrin-like and Metalloproteinase with Thromb...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5113859/ https://www.ncbi.nlm.nih.gov/pubmed/27855162 http://dx.doi.org/10.1371/journal.pbio.1002580 |
_version_ | 1782468253402005504 |
---|---|
author | McMahon, Meagan Ye, Siying Izzard, Leonard Dlugolenski, Daniel Tripp, Ralph A. Bean, Andrew G. D. McCulloch, Daniel R. Stambas, John |
author_facet | McMahon, Meagan Ye, Siying Izzard, Leonard Dlugolenski, Daniel Tripp, Ralph A. Bean, Andrew G. D. McCulloch, Daniel R. Stambas, John |
author_sort | McMahon, Meagan |
collection | PubMed |
description | The extracellular matrix (ECM) provides physical scaffolding for cellular constituents and initiates biochemical and biomechanical cues that are required for physiological activity of living tissues. The ECM enzyme ADAMTS5, a member of the ADAMTS (A Disintegrin-like and Metalloproteinase with Thrombospondin-1 motifs) protein family, cleaves large proteoglycans such as aggrecan, leading to the destruction of cartilage and osteoarthritis. However, its contribution to viral pathogenesis and immunity is currently undefined. Here, we use a combination of in vitro and in vivo models to show that ADAMTS5 enzymatic activity plays a key role in the development of influenza-specific immunity. Influenza virus infection of Adamts5(-/-) mice resulted in delayed virus clearance, compromised T cell migration and immunity and accumulation of versican, an ADAMTS5 proteoglycan substrate. Our research emphasises the importance of ADAMTS5 expression in the control of influenza virus infection and highlights the potential for development of ADAMTS5-based therapeutic strategies to reduce morbidity and mortality. |
format | Online Article Text |
id | pubmed-5113859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-51138592016-12-08 ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity McMahon, Meagan Ye, Siying Izzard, Leonard Dlugolenski, Daniel Tripp, Ralph A. Bean, Andrew G. D. McCulloch, Daniel R. Stambas, John PLoS Biol Research Article The extracellular matrix (ECM) provides physical scaffolding for cellular constituents and initiates biochemical and biomechanical cues that are required for physiological activity of living tissues. The ECM enzyme ADAMTS5, a member of the ADAMTS (A Disintegrin-like and Metalloproteinase with Thrombospondin-1 motifs) protein family, cleaves large proteoglycans such as aggrecan, leading to the destruction of cartilage and osteoarthritis. However, its contribution to viral pathogenesis and immunity is currently undefined. Here, we use a combination of in vitro and in vivo models to show that ADAMTS5 enzymatic activity plays a key role in the development of influenza-specific immunity. Influenza virus infection of Adamts5(-/-) mice resulted in delayed virus clearance, compromised T cell migration and immunity and accumulation of versican, an ADAMTS5 proteoglycan substrate. Our research emphasises the importance of ADAMTS5 expression in the control of influenza virus infection and highlights the potential for development of ADAMTS5-based therapeutic strategies to reduce morbidity and mortality. Public Library of Science 2016-11-17 /pmc/articles/PMC5113859/ /pubmed/27855162 http://dx.doi.org/10.1371/journal.pbio.1002580 Text en © 2016 McMahon et al 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 use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article McMahon, Meagan Ye, Siying Izzard, Leonard Dlugolenski, Daniel Tripp, Ralph A. Bean, Andrew G. D. McCulloch, Daniel R. Stambas, John ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity |
title | ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity |
title_full | ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity |
title_fullStr | ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity |
title_full_unstemmed | ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity |
title_short | ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity |
title_sort | adamts5 is a critical regulator of virus-specific t cell immunity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5113859/ https://www.ncbi.nlm.nih.gov/pubmed/27855162 http://dx.doi.org/10.1371/journal.pbio.1002580 |
work_keys_str_mv | AT mcmahonmeagan adamts5isacriticalregulatorofvirusspecifictcellimmunity AT yesiying adamts5isacriticalregulatorofvirusspecifictcellimmunity AT izzardleonard adamts5isacriticalregulatorofvirusspecifictcellimmunity AT dlugolenskidaniel adamts5isacriticalregulatorofvirusspecifictcellimmunity AT trippralpha adamts5isacriticalregulatorofvirusspecifictcellimmunity AT beanandrewgd adamts5isacriticalregulatorofvirusspecifictcellimmunity AT mccullochdanielr adamts5isacriticalregulatorofvirusspecifictcellimmunity AT stambasjohn adamts5isacriticalregulatorofvirusspecifictcellimmunity |