Molecular dynamics of chemokine receptors in memory T cells

为了揭示趋化因子受体的新功能，我们详细研究了CCR5和CXCR3在T细胞受体介导的信号传导中的作用。首次发现CCR5的表达是通过T细胞受体介导的激活诱导的，并且观察到CCR5及其配体RANTES颗粒在免疫突触中积累。利用CCR5-renilla和gfp - β -阻滞素，通过生物发光共振能量转移法（BRET）证明了CCR5通过TCR介导的信号通路激活。接下来，通过使用CCR5和CXCR3双敲除小鼠源性T淋巴细胞，证明CCR5和CXCR3在T细胞记忆反应中的关键作用。此外，通过CCR5、CXCR3单敲除和双敲除小鼠，证实CCR5而非CXCR3在ii型胶原诱导关节炎中的关键作用。这一结果提示CCR5可能成为类风湿关节炎的一个新的治疗靶点。

To disclose the novel function of chemokine receptors, the roles of CCR5 and CXCR3 in T cell receptor mediated signaling were in detail examined. The expression of CCR5 was first found to be induced by T cell receptor mediated activation, and CCR5 and its ligand RANTES granules were observed to be accumulated in the immunological synapse. The activation of CCR5 through TCR mediated signaling was proved by bioluminescence resonance energy transfer method (BRET) using CCR5-renilla and GFP-beta-arrestin. Next, The critical role of CCR5 and CXCR3 in T cell memory response was proved by using CCR5 and CXCR3 double knock out mice-derived T lymphocytes. Furthermore, The pivotal role of CCR5 but not CXCR3 in Type-II collagen induced arthritis was established using CCR5, CXCR3 single and double knock out mice. This result indicates that CCR5 could be a novel therapeutic target for rheumatoid arthritis.