Expression and function of discoidin domain receptor 1 in T cells

点击翻译按钮获取中文摘要

For an effective immune response and to reach target tissues, activated/effector T cells must overcome the barriers of the blood vessels as well as the extracellular matrix (ECM) of the basement membrane and of the interstitial stroma, which is constituted mainly of collagen. The use of three-dimensional (3D) models such as collagen gels revealed that activated T cells use the amoeboid movement to migrate in collagen independently from strong adhesive forces and integrins. In this regard, we and others previously reported that the discoidin domain receptor 1 (DDR1), a tyrosine kinase receptor, which binds collagens, is induced during T cell activation and participates in the migration of activated human T cells in 3D collagen. We recently demonstrated that the vast majority of human Th17 cells express DDR1 but not DDR2 and that silencing DDR1 or using the blocking recombinant receptor (DDR1:Fc) significantly reduced their migration in 3D collagen. DDR1 promoted amoeboid movement of Th17 cells by activating the RhoA/ROCK/MAPK/ERK signaling axis. Finally, we showed that DDR1 is important for the recruitment of Th17 cells in vivo (mouse air pouch model). The mechanisms of effector T cell migration in perivascular tissues are still poorly understood. Thus, based on our studies, we propose that DDR1 can be a major receptor in T cell migration and in the development of immune response.