Cargando…
Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway
Effector T cell migration through the tissue extracellular matrix (ECM) is an important step of the adaptive immune response and in the development of inflammatory diseases. However, the mechanisms involved in this process are still poorly understood. In this study, we addressed the role of a collag...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216699/ https://www.ncbi.nlm.nih.gov/pubmed/27391444 http://dx.doi.org/10.18632/oncotarget.10455 |
_version_ | 1782491962722484224 |
---|---|
author | Azreq, Mohammed-Amine El Kadiri, Maleck Boisvert, Marc Pagé, Nathalie Tessier, Philippe A. Aoudjit, Fawzi |
author_facet | Azreq, Mohammed-Amine El Kadiri, Maleck Boisvert, Marc Pagé, Nathalie Tessier, Philippe A. Aoudjit, Fawzi |
author_sort | Azreq, Mohammed-Amine El |
collection | PubMed |
description | Effector T cell migration through the tissue extracellular matrix (ECM) is an important step of the adaptive immune response and in the development of inflammatory diseases. However, the mechanisms involved in this process are still poorly understood. In this study, we addressed the role of a collagen receptor, the discoidin domain receptor 1 (DDR1), in the migration of Th17 cells. We showed that the vast majority of human Th17 cells express DDR1 and that silencing DDR1 or using the blocking recombinant receptor DDR1:Fc significantly reduced their motility and invasion in three-dimensional (3D) collagen. DDR1 promoted Th17 migration by activating RhoA/ROCK and MAPK/ERK signaling pathways. Interestingly, the RhoA/ROCK signaling module was required for MAPK/ERK activation. Finally, we showed that DDR1 is important for the recruitment of Th17 cells into the mouse dorsal air pouch containing the chemoattractant CCL20. Collectively, our results indicate that DDR1, via the activation of RhoA/ROCK/MAPK/ERK signaling axis, is a key pathway of effector T cell migration through collagen of perivascular tissues. As such, DDR1 can contribute to the development of Th17-dependent inflammatory diseases. |
format | Online Article Text |
id | pubmed-5216699 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-52166992017-01-15 Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway Azreq, Mohammed-Amine El Kadiri, Maleck Boisvert, Marc Pagé, Nathalie Tessier, Philippe A. Aoudjit, Fawzi Oncotarget Research Paper: Immunology Effector T cell migration through the tissue extracellular matrix (ECM) is an important step of the adaptive immune response and in the development of inflammatory diseases. However, the mechanisms involved in this process are still poorly understood. In this study, we addressed the role of a collagen receptor, the discoidin domain receptor 1 (DDR1), in the migration of Th17 cells. We showed that the vast majority of human Th17 cells express DDR1 and that silencing DDR1 or using the blocking recombinant receptor DDR1:Fc significantly reduced their motility and invasion in three-dimensional (3D) collagen. DDR1 promoted Th17 migration by activating RhoA/ROCK and MAPK/ERK signaling pathways. Interestingly, the RhoA/ROCK signaling module was required for MAPK/ERK activation. Finally, we showed that DDR1 is important for the recruitment of Th17 cells into the mouse dorsal air pouch containing the chemoattractant CCL20. Collectively, our results indicate that DDR1, via the activation of RhoA/ROCK/MAPK/ERK signaling axis, is a key pathway of effector T cell migration through collagen of perivascular tissues. As such, DDR1 can contribute to the development of Th17-dependent inflammatory diseases. Impact Journals LLC 2016-07-06 /pmc/articles/PMC5216699/ /pubmed/27391444 http://dx.doi.org/10.18632/oncotarget.10455 Text en Copyright: © 2016 Azreq et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper: Immunology Azreq, Mohammed-Amine El Kadiri, Maleck Boisvert, Marc Pagé, Nathalie Tessier, Philippe A. Aoudjit, Fawzi Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway |
title | Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway |
title_full | Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway |
title_fullStr | Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway |
title_full_unstemmed | Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway |
title_short | Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway |
title_sort | discoidin domain receptor 1 promotes th17 cell migration by activating the rhoa/rock/mapk/erk signaling pathway |
topic | Research Paper: Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216699/ https://www.ncbi.nlm.nih.gov/pubmed/27391444 http://dx.doi.org/10.18632/oncotarget.10455 |
work_keys_str_mv | AT azreqmohammedamineel discoidindomainreceptor1promotesth17cellmigrationbyactivatingtherhoarockmapkerksignalingpathway AT kadirimaleck discoidindomainreceptor1promotesth17cellmigrationbyactivatingtherhoarockmapkerksignalingpathway AT boisvertmarc discoidindomainreceptor1promotesth17cellmigrationbyactivatingtherhoarockmapkerksignalingpathway AT pagenathalie discoidindomainreceptor1promotesth17cellmigrationbyactivatingtherhoarockmapkerksignalingpathway AT tessierphilippea discoidindomainreceptor1promotesth17cellmigrationbyactivatingtherhoarockmapkerksignalingpathway AT aoudjitfawzi discoidindomainreceptor1promotesth17cellmigrationbyactivatingtherhoarockmapkerksignalingpathway |