期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 30, 页码 17510-17512出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1921324117
关键词
type I interferon; endosome; cytokine retention
资金
- New York University [AG08051, R01AF058267]
- Deutsche Forschungsgemeinschaft [PI 405/10, PI 405/14]
- National Institute of Allergy and Infectious Diseases [R01AI127372]
- Virus-Host Interactions training grant [5T32AI007647-17]
Type I IFN (IFN-I) is thought to be rapidly internalized and degraded following binding to its receptor and initiation of signaling. However, many studies report the persistent effects mediated by IFN-I for days or even weeks, both ex vivo and in vivo. These long-lasting effects are attributed to downstream signaling molecules or induced effectors having a long half-life, particularly in specific cell types. Here, we describe a mechanism explaining the long-term effects of IFN-I. Following receptor binding, IFN-I is siloed into endosomal compartments. These intracellular IFN silos persist for days and can be visualized by fluorescence and electron microscopy. However, they are largely dormant functionally, due to IFN-I-induced negative regulators. By contrast, in individuals lacking these negative regulators, such as ISG15 or USP18, this siloed IFN-I can continue to signal from within the endosome. This mechanism may underlie the long-term effects of IFN-I therapy and may contribute to the pathophysiology of type I interferonopathies.
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