title: Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway.
abstract: 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.
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, QC, Canada.
authors.forename: Mohammed-Amine
authors.initials: MA
authors.lastname: El Azreq
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, QC, Canada.
authors.forename: Maleck
authors.initials: M
authors.lastname: Kadiri
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, QC, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Boisvert
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, QC, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pagé
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, QC, Canada.|Département de Microbiologie-Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Tessier
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, QC, Canada.|Département de Microbiologie-Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Fawzi
authors.initials: F
authors.lastname: Aoudjit
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D000070819:Discoidin Domain Receptor 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000502:physiology; D058504:Th17 Cells / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000070819:Discoidin Domain Receptor 1; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
keywords: 3D collagen; DDR1; Immune response; Immunology and Microbiology Section; RhoA/ROCK; Th17 cells; migration