The CXCL12 system is central to the development of many organs and is further crucially engaged in pathophysiological processes underlying cancer, inflammation, and cardiovascular disorders. This disease-associated role presently focuses major interest on the two CXCL12 receptors, CXCR4 and atypical chemokine receptor 3 (ACKR3)/CXCR7, as promising therapeutic targets. Major obstacles in these ongoing efforts are confusing reports on the differential use of either ACKR3/CXCR7 and/or CXCR4 across various cells as well as on the specific function(s) of ACKR3/CXCR7. Although basically no doubts remain that CXCR4 represents a classic chemokine receptor, functions assigned to ACKR3/CXCR7 range from those of a strictly silent scavenger receptor eventually modulating CXCR4 signaling to an active and independent signaling receptor. In this review, we depict a thorough analysis of our present knowledge on different modes of organization and functions of the cellular CXCL12 system. We further highlight the potential role of ACKR3/CXCR7 as a “crosslinker” of different receptor systems. Finally, we discuss mechanisms with the potency to impinge on the cellular organization of the CXCL12 system and hence might represent additional future therapeutic targets.

中文翻译：

---

CXCL12受体ACKR3 / CXCR7的功能-被感知和被忽视的内容。

CXCL12系统对许多器官的发育至关重要，并且进一步至关重要地参与了癌症，炎症和心血管疾病的病理生理过程。目前，这种与疾病相关的作用主要集中在两个有前景的治疗靶点CXCL12受体CXCR4和非典型趋化因子受体3（ACKR3）/ CXCR7上。这些正在进行的工作中的主要障碍是，关于跨各种单元不同使用ACKR3 / CXCR7和/或CXCR4以及关于ACKR3 / CXCR7的特定功能的报告令人困惑。尽管基本上没有疑问，CXCR4代表经典的趋化因子受体，但分配给ACKR3 / CXCR7的功能范围从严格沉默的清道夫受体的功能开始，最终将CXCR4信号传导调节为主动和独立的信号传导受体。在这篇评论中 我们描绘了我们对蜂窝CXCL12系统的不同组织和功能模式的现有知识的透彻分析。我们进一步强调了ACKR3 / CXCR7作为不同受体系统的“交联剂”的潜在作用。最后，我们讨论了可能影响CXCL12系统细胞组织的机制，因此可能代表了未来的其他治疗靶标。