期刊
MOLECULAR CELL
卷 66, 期 5, 页码 635-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2017.05.011
关键词
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资金
- U.S.-Israel Binational Science Foundation [2012327]
- US National Institutes of Health [R01-AI083408]
- Intramural Research programs of the NHLBI, NIH
- Center for Cancer Research, NCI, NIH
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 acuteimmune 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 gamma (IFN gamma) by combining a systems-scale analysis of gene expression dynamics with computational modeling and experiments. We discovered that IFN gamma 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 in new immunotherapies targeting PS and inflammatory pathways.
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