Abstract
The production of type I interferon (IFN) is precisely modulated by host to protect against viral infection efficiently without obvious immune disorders. Elucidating the tight control towards type I IFN production would be helpful to get insight into natural immunity and inflammatory diseases. As yet, however, the mechanisms that regulate IFN-β production, especially the epigenetic regulatory mechanisms, remain poorly explored. This study elucidated the potential function of Peptidylarginine deiminases (PADIs)-mediated citrullination in innate immunity. We identified PADI4, a PADIs family member that can act as an epigenetic coactivator, could repress IFN-β production upon RNA virus infection. Detailed experiments showed that PADI4 deficiency increased IFN-β production and promoted antiviral immune activities against RNA viruses. Mechanistically, the increased PADI4 following viral infection translocated to nucleus and recruited HDAC1 upon binding to Ifnb1 promoter, which then led to the deacetylation of histone H3 and histone H4 for repressing Ifnb1 transcription. Taken together, we identify a novel non-classical role for PADI4 in the regulation of IFN-β production, suggesting its potential as treatment target in inflammatory or autoimmune diseases.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Biochimica et biophysica acta. Molecular basis of disease
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
