{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["31(3)"],"submitter":["Jiao H"],"pubmed_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."],"journal":["Cell death and differentiation"],"pagination":["280-291"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10923883"],"repository":["biostudies-literature"],"pubmed_title":["DUSP4 modulates RIG-I- and STING-mediated IRF3-type I IFN response."],"pmcid":["PMC10923883"],"pubmed_authors":["Li H","Chu JJH","James SJ","Renia L","Png CW","Wang H","Li L","Jiao H","Min N","Li W","Claser C","Chen MI","Zhang Y","Chia WN","Cui C","Tan KSW","Deng Y"],"additional_accession":[]},"is_claimable":false,"name":"DUSP4 modulates RIG-I- and STING-mediated IRF3-type I IFN response.","description":"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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-27T03:08:12.457Z","creation":"2026-06-27T03:05:21.752Z"},"accession":"S-EPMC10923883","cross_references":{"pubmed":["38383887"],"doi":["10.1038/s41418-024-01269-7"]}}