趋化因子通过经典 G 蛋白偶联受体 (GPCR) 发出信号，在发育、免疫稳态和多种疾病过程中诱导细胞迁移。在过去的十年中，非典型趋化因子受体 (ACKR) 的一个亚家族从 GPCR 中被描述出来，因为它们无法触发传统的 G 蛋白信号传导或介导细胞迁移以响应趋化因子。然而，这些受体通过隔离、运输或内化趋化因子，从而调节其可用性并塑造其梯度，从而在趋化因子系统中发挥重要作用。 GPR182 是最近去孤儿化的趋化因子受体，与其最接近的 ACKR3 具有约 30% 的序列相似性。 GPR182 主要在内皮细胞上表达，被认为可作为清除剂调节来自 CXC、CC 和 XC 家族的大量趋化因子的可用性，并与 ACKR3 和 ACKR4 协同作用。与其他 ACKR 不同，GPR182 与 β-arrestins 具有很强的本构性相互作用，这是细胞内受体运输和趋化因子清除所必需的。 GPR182 的趋化因子连接对 β-抑制蛋白募集没有额外可检测到的影响。 GPR182 的基因消除会影响脾脏大小、骨髓生成和血清趋化因子水平，表明其在趋化因子稳态和免疫调节中的作用。据报道，GPR182 还可以调节对血源性抗原的免疫反应和肿瘤发生。总而言之，令人信服的累积证据表明，GPR182 不会触发 G 蛋白介导的信号传导，而是在体外和体内充当趋化因子的清除剂，强烈支持将其作为 ACKR5 纳入趋化因子受体的系统命名法中。意义声明 所总结的发现强烈支持将 GPR182 指定为 ACKR5 及其正式纳入非典型趋化因子受体家族。

Chemokines signal through classical G protein-coupled receptors (GPCRs) to induce cell migration during development, immune homeostasis and multiple diseases. Over the last decade a subfamily of atypical chemokine receptors (ACKRs) was delineated from GPCRs based on their inability to trigger conventional G protein signaling or mediate cell migration in response to chemokines. These receptors nevertheless play an important role within the chemokine system by sequestering, transporting or internalizing chemokines thereby regulating their availability and shaping their gradients. GPR182, the recently deorphanized chemokine receptor, shares about 30% of sequence similarity with its closest relative ACKR3. GPR182 is mainly expressed on endothelial cells and was proposed to act as a scavenger regulating the availability of a large set of chemokines from the CXC, CC and XC families and to act cooperatively with ACKR3 and ACKR4. Unlike other ACKRs, GPR182 was shown to have a strong constitutive interaction with β-arrestins that is required for intracellular receptor trafficking and chemokine scavenging. Chemokine ligation of GPR182 has no additional detectable impact on β-arrestin recruitment. Genetic ablation of GPR182 affects spleen size, myelopoiesis, and serum chemokine levels, indicating its role in chemokine homeostasis and immune regulation. GPR182 was also reported to regulate immune responses to bloodborne antigens and tumorigenesis. Taken together, compelling cumulative evidence indicates that GPR182 does not trigger G protein-mediated signaling but acts as a scavenger for chemokines in vitro and in vivo strongly supporting its inclusion as ACKR5 in the systematic nomenclature of chemokine receptors. Significance Statement The summarized presented findings strongly support the designation of GPR182 as ACKR5 and its formal inclusion in the family of atypical chemokine receptors.