DUSP4 modulates RIG-I- and STING-mediated IRF3-type I IFN response.
Cell Death Differ
; 31(3): 280-291, 2024 03.
Article
en En
| MEDLINE
| ID: mdl-38383887
ABSTRACT
Detection of cytosolic nucleic acids by pattern recognition receptors, including STING and RIG-I, leads to the activation of multiple signalling pathways that culminate in the production of type I interferons (IFNs) which are vital for host survival during virus infection. In addition to protective immune modulatory functions, type I IFNs are also associated with autoimmune diseases. Hence, it is important to elucidate the mechanisms that govern their expression. In this study, we identified a critical regulatory function of the DUSP4 phosphatase in innate immune signalling. We found that DUSP4 regulates the activation of TBK1 and ERK1/2 in a signalling complex containing DUSP4, TBK1, ERK1/2 and IRF3 to regulate the production of type I IFNs. Mice deficient in DUSP4 were more resistant to infections by both RNA and DNA viruses but more susceptible to malaria parasites. Therefore, our study establishes DUSP4 as a regulator of nucleic acid sensor signalling and sheds light on an important facet of the type I IFN regulatory system.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Virosis
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Interferón Tipo I
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Proteínas Tirosina Fosfatasas
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Receptores de Superficie Celular
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Proteínas Roundabout
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Proteínas de la Membrana
Idioma:
En
Revista:
Cell Death Differ
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Cell death and differentiation
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Cell death differ
Año:
2024
Tipo del documento:
Article