Catch and Release of Cytokines Mediated by Tumor Phosphatidylserine Converts Transient Exposure into Long-Lived Inflammation.
Catch and Release of Cytokines Mediated by Tumor Phosphatidylserine Converts Transient Exposure into Long-Lived Inflammation.
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DOI：
10.1016/j.molcel.2017.05.011
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发表时间：
2017-06-01
期刊：
影响因子：
16
通讯作者：
Altan-Bonnet G
中科院分区：
文献类型：
--
作者：
Oyler-Yaniv J;Oyler-Yaniv A;Shakiba M;Min NK;Chen YH;Cheng SY;Krichevsky O;Altan-Bonnet N;Altan-Bonnet G
免疫细胞不断地调查宿主是否存在病原体或肿瘤，并分泌细胞因子来警告周围细胞这些威胁。在体内，激活的免疫细胞会分泌细胞因子数小时，但急性免疫反应会在数天内发生。考虑到这些不同的时间尺度，我们讨论了细胞因子反应性细胞如何将短暂的细胞因子暴露转化为长期持续的表型变化。我们通过将基因表达动力学的系统规模分析与计算模型和实验相结合，研究了黑色素瘤细胞对细胞因子干扰素 γ (IFNγ) 短暂暴露的反应。我们发现IFNγ在体外和体内均被活细胞表面的磷脂酰丝氨酸（PS）捕获，然后缓慢释放以驱动细胞因子反应基因的长期转录。这种机制为 PS 引入了动态调节不同癌症和原代细胞类型炎症的额外功能，并有可能带来针对 PS 和炎症途径的新免疫疗法。激活的免疫细胞会分泌细胞因子数小时，但急性免疫反应会在一周或更长时间内发生。奥勒-亚尼夫等人。通过揭示癌症和免疫细胞如何依赖其表面磷脂酰丝氨酸捕获细胞因子，然后缓慢释放它们并引发长期的细胞间通讯，解决了这种时间尺度的差异。
Immune cells constantly survey the host for pathogens or tumors and secrete cytokines to alert surrounding cells of these threats. In vivo, activated immune cells secrete cytokines for several hours, yet an acute immune reaction occurs over days. Given these divergent timescales, we addressed how cytokine-responsive cells translate brief cytokine exposure into phenotypic changes that persist over long timescales. We studied melanoma cell responses to transient exposure to the cytokine Interferon γ (IFNγ) by combining a systems-scale analysis of gene expression dynamics with computational modeling and experiments. We discovered that IFNγ is captured by phosphatidylserine (PS) on the surface of viable cells both in vitro and in vivo, then slowly released to drive long-term transcription of cytokine-response genes. This mechanism introduces an additional function for PS in dynamically regulating inflammation across diverse cancer and primary cell types, and has potential to usher new immunotherapies targeting PS and inflammatory pathways. Activated immune cells secrete cytokines for few hours, yet acute immune reactions unfold over a week or more. Oyler-Yaniv et al. resolve this timescale discrepancy by uncovering how cancer & immune cells rely on their surface phosphatidylserine to capture cytokines then slowly release them and elicit long-term cell-to-cell communication.
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影响因子：
32.4
作者：
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影响因子：
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