Expression and function of discoidin domain receptor 1 in T cells

为了有效的免疫应答和到达靶组织，激活/效应T细胞必须克服血管以及基底膜和间质基质的细胞外基质(ECM)的屏障，这些屏障主要由胶原组成。使用三维(3D)模型，如胶原胶，发现激活的T细胞利用变形虫运动独立于强大的粘附力和整合素迁移到胶原蛋白中。在这方面，我们和其他人以前报道过，盘状结构域受体1(DDR1)是一种结合胶原蛋白的酪氨酸激酶受体，在T细胞激活过程中被诱导，并参与激活的人T细胞在3D胶原中的迁移。我们最近证实，绝大多数人Th17细胞表达DDR1，但不表达DDR2，并且沉默DDR1或使用阻断的重组受体(DDR1：Fc)显著减少它们在3D胶原中的迁移。DDR1通过激活RhoA/ROCK/MAPK/ERK信号轴促进Th17细胞的阿米巴运动。最后，我们证明了DDR1对于Th17细胞在体内(小鼠气囊模型)的募集是重要的。效应性T细胞在血管周围组织中的迁移机制尚不清楚。因此，根据我们的研究，我们认为DDR1可能是T细胞迁移和免疫反应发展的主要受体。

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.