CXCR4-CCR5: A couple modulating T cell functions
CXCR4-CCR5: A couple modulating T cell functions
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DOI：
10.1073/pnas.0804286105
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发表时间：
2008-07-22
影响因子：
11.1
通讯作者：
Viola, Antonella
中科院分区：
文献类型：
--
作者：
Contento, Rita Lucia;Molon, Barbara;Viola, Antonella
趋化因子及其受体指导白细胞在血液、淋巴和组织中的迁移。最近积累的证据表明，除了趋化功能外，趋化因子受体是高度通用的参与者，可以微调免疫反应。在抗原呈递细胞激活人类T细胞的过程中，趋化因子受体CCR5和CXCR4被招募到免疫突触中，在那里它们传递共刺激信号。然而，允许趋化因子受体信号通用性的分子机制尚不清楚。在这里，我们描述了CXCR4和CCR5之间的功能相互作用，以发挥特定的生物学功能并调节T淋巴细胞反应。我们证明CCR5和CXCR4之间的同时表达和合作是趋化因子诱导的免疫突触T细胞共刺激所必需的。此外，我们还提供了两种受体在激活不同T细胞功能的信号复合体中的物理关联的证据。我们认为受体之间的合作是趋化因子功能可塑性的一个关键策略。
Chemokines and their receptors direct leukocyte migration among blood, lymph and tissues. Evidence has recently accumulated that, besides their chemotactic functions, chemokine receptors are highly versatile players that fine tune immune responses. During human T cell activation by antigen-presenting cells, the chemokine receptors CCR5 and CXCR4 are recruited into the immunological synapse, where they deliver costimulatory signals. However, the molecular mechanisms allowing signaling versatility of chemokine receptors are unknown. Here, we describe the functional interaction between CXCR4 and CCR5 to exert specific biological functions and modulate T lymphocyte responses. We demonstrate that simultaneous expression and cooperation between CCR5 and CXCR4 are required for chemokine-induced T cell costimulation at the immunological synapse. In addition, we provide evidence for a physical association of the two receptors in a signaling complex that activates distinct T cell functions. We suggest that cooperation between receptors represents one key strategy for the functional plasticity of chemokines.