Identification of human CCR8 as a CCL18 receptor.
Identification of human CCR8 as a CCL18 receptor.
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DOI：
10.1084/jem.20130240
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发表时间：
2013-09-23
期刊：
影响因子：
--
通讯作者：
Luster AD
中科院分区：
文献类型：
--
作者：
Islam SA;Ling MF;Leung J;Shreffler WG;Luster AD
CCL18是人CCR8受体的内源性激动剂。CC趋化因子配体18（CCL18）是人类慢性炎症性疾病中最高表达的趋化因子之一。由于缺乏已鉴定的趋化因子受体，对CCL18在这些疾病中的作用的认识受到阻碍。我们报道了人趋化因子受体CCR8是一种CCL18受体。CCL18诱导人CCR8转染细胞的趋化性和钙流。CCL18以高亲和力结合CCR8并诱导其内化。人CCL1（已知的内源性CCR8配体）和CCL18竞争结合CCR8转染的细胞。此外，CCL1和CCL18诱导CCR8转染细胞和人Th2细胞的异源交叉脱敏。CCL18通过CCR8诱导人活化的高度极化的Th2细胞的趋化性和钙流。野生型而非Ccr8缺陷型活化的小鼠Th2细胞响应于CCL18而迁移。CCL18和CCR8在患有活动性嗜酸性食管炎（EoE）的个体的食管活检组织中共表达，并且与从疾病处于缓解期的EoE患者或正常对照中分离的食管组织相比，CCL18和CCR8以显著更高的水平存在。将CCR8鉴定为CCL18的趋化因子受体将有助于阐明这种高度表达的趋化因子在人类疾病中的生物学作用。
CCL18 is an endogenous agonist of the human CCR8 receptor. The CC chemokine ligand 18 (CCL18) is one of the most highly expressed chemokines in human chronic inflammatory diseases. An appreciation of the role of CCL18 in these diseases has been hampered by the lack of an identified chemokine receptor. We report that the human chemokine receptor CCR8 is a CCL18 receptor. CCL18 induced chemotaxis and calcium flux of human CCR8-transfected cells. CCL18 bound with high affinity to CCR8 and induced its internalization. Human CCL1, the known endogenous CCR8 ligand, and CCL18 competed for binding to CCR8-transfected cells. Further, CCL1 and CCL18 induced heterologous cross-desensitization of CCR8-transfected cells and human Th2 cells. CCL18 induced chemotaxis and calcium flux of human activated highly polarized Th2 cells through CCR8. Wild-type but not Ccr8-deficient activated mouse Th2 cells migrated in response to CCL18. CCL18 and CCR8 were coexpressed in esophageal biopsy tissue from individuals with active eosinophilic esophagitis (EoE) and were present at markedly higher levels compared with esophageal tissue isolated from EoE patients whose disease was in remission or in normal controls. Identifying CCR8 as a chemokine receptor for CCL18 will help clarify the biological role of this highly expressed chemokine in human disease.
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作者：
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