Research Papers: Immunology:

Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway

Mohammed-Amine El Azreq, Maleck Kadiri, Marc Boisvert, Nathalie Pagé, Philippe A. Tessier and Fawzi Aoudjit _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:44975-44990. https://doi.org/10.18632/oncotarget.10455

Metrics: PDF 3022 views  |   HTML 4593 views  |   ?  


Mohammed-Amine El Azreq1, Maleck Kadiri1, Marc Boisvert1, Nathalie Pagé1, Philippe A. Tessier1,2 and Fawzi Aoudjit1,2

1 Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, QC, Canada

2 Département de Microbiologie-Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada

Correspondence to:

Fawzi Aoudjit, email:

Keywords: Th17 cells; migration; DDR1; 3D collagen; RhoA/ROCK; Immunology and Microbiology Section, Immune response, Immunity

Received: February 24, 2016 Accepted: June 13, 2016 Published: July 06, 2016


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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 10455