Type I IFN is siloed in endosomes.
cytokine retention
endosome
type I interferon
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
28 07 2020
28 07 2020
Historique:
pubmed:
16
7
2020
medline:
18
9
2020
entrez:
16
7
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32665439
pii: 1921324117
doi: 10.1073/pnas.1921324117
pmc: PMC7395562
doi:
Substances chimiques
Cytokines
0
Interferon Type I
0
Ubiquitins
0
ISG15 protein, human
60267-61-0
USP18 protein, human
EC 3.4.19.12
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
17510-17512Subventions
Organisme : NIA NIH HHS
ID : P30 AG008051
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127372
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007647
Pays : United States
Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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