title: Human Th17 Migration in Three-Dimensional Collagen Involves p38 MAPK.
abstract: T cell migration across extracellular matrix (ECM) is an important step of the adaptive immune response but is also involved in the development of inflammatory autoimmune diseases. Currently, the molecular mechanisms regulating the motility of effector T cells in ECM are not fully understood. Activation of p38 MAPK has been implicated in T cell activation and is critical to the development of immune and inflammatory responses. In this study, we examined the implication of p38 MAPK in regulating the migration of human Th17 cells through collagen. Using specific inhibitor and siRNA, we found that p38 is necessary for human Th17 migration in three-dimensional (3D) collagen and that 3D collagen increases p38 phosphorylation. We also provide evidence that the collagen receptor, discoidin domain receptor 1 (DDR1), which promotes Th17 migration in 3D collagen, is involved in p38 activation. Together, our findings suggest that targeting DDR1/p38 MAPK pathway could be beneficial for the treatment of Th17-mediated inflammatory diseases. J. Cell. Biochem. 118: 2819-2827, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, Quebec, 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, Quebec, 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, Quebec, Canada.
authors.forename: Sofiane
authors.initials: S
authors.lastname: Berrazouane
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, Quebec, 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, Quebec, Canada.|Département de Microbiologie-Immunologie, Faculté de Médecine, Université Laval, Québec, Quebec, Canada.
authors.forename: Fawzi
authors.initials: F
authors.lastname: Aoudjit
mesh_terms: D002465:Cell Movement / Q000276:immunology*; D003094:Collagen / Q000737:chemistry*; D000070819:Discoidin Domain Receptor 1 / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology*
chemical_list: D003094:Collagen; C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1; D048051:p38 Mitogen-Activated Protein Kinases
keywords: 3D COLLAGEN; DDR1; MIGRATION; T CELLS; p38 MAPK