Type I IFN is siloed in endosomes
Autor(en): | Altman, Jennie B. Taft, Justin Wedeking, Tim Gruber, Conor N. Holtmannspoetter, Michael Piehler, Jacob Bogunovic, Dusan |
Stichwörter: | cytokine retention; endosome; INTERFERONS; Multidisciplinary Sciences; Science & Technology - Other Topics; type I interferon | Erscheinungsdatum: | 2020 | Herausgeber: | NATL ACAD SCIENCES | Journal: | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | Volumen: | 117 | Ausgabe: | 30 | Startseite: | 17510 | Seitenende: | 17512 | Zusammenfassung: | 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. |
ISSN: | 00278424 | DOI: | 10.1073/pnas.1921324117 |
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geprüft am 03.05.2024