title: Discoidin domain receptor 1 expression in activated T cells is regulated by the ERK MAP kinase signaling pathway.
abstract: The expression and function of discoidin domain receptor 1 (DDR1) in T cells are still poorly explored. We have recently shown that activation of primary human T cells via their T cell receptor leads to increased expression of DDR1, which promoted their migration in three-dimensional collagen. In the present study, we provide evidence that activated T cells bind collagen through DDR1. We found that the DDR1:Fc blocking molecule significantly reduced the ability of activated T cells to bind soluble biotinylated collagen. However, DDR1:Fc had no impact on the adhesion of activated T cells to collagen and overexpression of DDR1 in Jurkat T cells did not enhance their adhesion. Together, our results indicate that DDR1 can promote T cell migration without enhancing adhesion to collagen, suggesting that it can contribute to the previously described amoeboid movement of activated T cells in collagen matrices. Our results also show that CD28, in contrast to IL-2 expression, did not costimulate the expression of DDR1 in primary human T cells. Using specific inhibitors, we demonstrated that TCR-induced expression of DDR1 in T cells is regulated by the Ras/Raf/ERK MAP Kinase and PKC pathways but not by calcium/calcineurin signaling pathway or the JNK and P38 MAP Kinases. Thus, our study provides additional insights into the physiology of DDR1 in T cells and may therefore further our understanding of the regulatory mechanisms of T cell migration.
authors.affiliation: Centre de Recherche en Rhumatologie-Immunologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, and Faculté de Médecine, Université Laval, 2705 Blvd Laurier, Local T1-49, Québec, QC, Canada G1V 4G2.
authors.forename: Nizar
authors.initials: N
authors.lastname: Chetoui
authors.forename: Mohammed-Amine
authors.initials: MA
authors.lastname: El Azreq
authors.forename: Marc
authors.initials: M
authors.lastname: Boisvert
authors.forename: Marie-Ève
authors.initials: MÈ
authors.lastname: Bergeron
authors.forename: Fawzi
authors.initials: F
authors.lastname: Aoudjit
mesh_terms: D020013:Calcium Signaling; D000070818:Discoidin Domain Receptors; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D016133:Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases