1. Hypersensitivity to type I interferon as a cause of hydrocephalus development.
- Author
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Arimoto KI, Zhang Y, Matsuura S, Miyauchi S, and Zhang DE
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Signal Transduction drug effects, Brain metabolism, Brain pathology, Brain drug effects, Ependyma metabolism, Cell Proliferation drug effects, Pyroptosis drug effects, Pyroptosis physiology, Hydrocephalus genetics, Hydrocephalus pathology, Mice, Knockout, Interferon Type I metabolism, Ubiquitin Thiolesterase genetics, Ubiquitin Thiolesterase metabolism, Receptor, Interferon alpha-beta genetics, Receptor, Interferon alpha-beta metabolism
- Abstract
Ubiquitin specific protease 18 (USP18) serves as a potent inhibitor of Type I interferon (IFN) signaling. Previous studies have shown that Usp18 deficient (homozygous Usp18 gene knockout) mice exhibit hydrocephalus; however, the precise molecular mechanism underlying hydrocephalus development remains elusive. In this study, we demonstrate that mice lacking both type I IFN receptor subunit 1 (Ifnar1) and Usp18 (Ifnar1/Usp18 double knockout mice) are viable and do not display a hydrocephalus phenotype. Moreover, we observed that suppression of USP18 in ependymal cells treated with IFN significantly increased cell death, including pyroptosis, and decreased proliferation. These findings suggest that heightened sensitivity to type I IFN during brain development contributes to the onset of hydrocephalus. Furthermore, they imply that inhibition of IFN signaling may hold promise as a therapeutic strategy for hydrocephalus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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