IRF11 synergizes with STAT1 and STAT2 to promote type I IFN production

• Published in: Fish & shellfish immunology Vol. 150; p. 109656
• Main Authors: Jiao, Zhiyuan, Li, Wenxing, Xiang, Chao, Li, DongLi, Huang, Wenshu, Nie, Pin, Huang, Bei
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2024
• Subjects: Anguilla - genetics; Anguilla - immunology; Animals; Fish Diseases - immunology; Fish Proteins - genetics; Fish Proteins - immunology; Fish Proteins - metabolism; Gene Expression Regulation - immunology; IFN production; Immunity, Innate - genetics; Interferon regulatory factor; Interferon Regulatory Factors - genetics; Interferon Regulatory Factors - immunology; Interferon Regulatory Factors - metabolism; Interferon Type I - genetics; Interferon Type I - immunology; IRF11; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - metabolism; STAT2 Transcription Factor - genetics; STAT2 Transcription Factor - metabolism; STATs; Zebrafish - genetics; Zebrafish - immunology; IFN production; IRF11; Interferon regulatory factor; STATs
• ISSN: 1050-4648; 1095-9947; 1095-9947
• DOI: 10.1016/j.fsi.2024.109656

Interferon regulatory factor 11 (IRF11), a fish specific member of IRF family, is a transcription factor known for its positive role in teleost antiviral defense by regulating IFN expression. Despite its recognized function, the precise mechanism of IRF11 in type I IFNs production remains largely unknown. In this study, we identified IRF11 in Japanese eel, Anguilla japonica, (AjIRF11) and determined its involvement in the later phase of fish IFN production. Our results demonstrate that IRF11-induced IFN production operates through ISRE binding. Mutations in each ISRE site within the promoter of AjIFN2 or AjIFN4 abolished IRF11-mediated activation of IFN promoters. In addition, the overexpression of AjIRF11 does not significantly impact the activation of AjIFN promoters induced by RLR-related signaling pathway proteins. Furthermore, IRF11-knockdown in ZFLs (zebrafish liver cells) has no effect on the RLRs-induced expression of zebrafish IFN-φ1 and IFN-φ3, indicating that IRF11 is not involved in the RLR-mediated IFN production. However, AjIRF11 can form transcription complexes with AjSTAT1 or AjSTAT2, or form homo- or heterodimers with AjIRF1 to stimulate the transcription of type I IFNs. Overall, it is shown in this study that IRF11 can act synergistically with STAT1 and/or STAT2 for the induction of IFN. •IRF11-induced activation of AjIFN2 and AjIFN4 is mediated through all ISRE sites.•IRF11-mediated IFN activation is independent of RLR pathway.•IRF11 formed transcription complexes with STAT1 or STAT2 to active IFN production.