Grass carp (Ctenopharyngodon idella) interferon regulatory factor 8 down-regulates interferon1 expression via interaction with interferon regulatory factor 2 in vitro. (September 2021)

• Record Type: Journal Article
• Authors: Chang, Kaile; Han, Kun; Qiu, Weihua; Hu, Zhizhen; Chen, Xingxing; Chen, Xin; Xie, Xiaofen; Wang, Shanghong; Hu, Chengyu; Mao, Huiling
• Is Part Of: Molecular immunology. Volume 137(2021)
• Page Start: 202
• Page End: 211
• Publication Date: 2021-09
• Subjects: IRF8 -- IRF2 -- IFN1 transcription -- Negative regulation -- Fish; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2021.04.020
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: CiIRF8 can respond to poly(I:C) stimulation. poly(I:C) facilitates the nuclear translocation of CiIRF8. Interaction between CiIRF8 and CiIRF2 following poly(I:C) stimulation. CiIRF8 and CiIRF2 synergistically down-regulates the transcription of Ciifn1 . CiIRF1 alleviates the transcription inhibition of Ciifn1 by competitive combination with CiIRF2 or CiIRF8. Abstract: Interferon regulatory factor 8 (IRF8), also known as interferon consensus sequence-binding protein (ICSBP), is a negative regulatory factor of interferon (IFN) and plays an important role in cell differentiation and innate immunity in mammals. In recent years, some irf 8 homologous genes have been cloned and confirmed to take part in innate immune response in fish, but the mechanism still remains unclear. In this paper, a grass carp ( Ctenopharyngodon idella ) irf8 gene ( Ciirf8 ) was cloned and characterized. The deduced protein (CiIRF8) possesses a highly conserved N-terminal DNA binding domain but a less well-conserved C-terminal IRF association domain (IAD). Ciirf8 was widely expressed in all tested tissues of grass carp and up-regulated following poly(I:C) stimulation. Ciirf8 expression was also up-regulated in CIK cells upon treatment with poly(I:C). To explore the molecular mechanism of how fish IRF8 regulates ifn1 expression, the similarities and differences of grass carp IRF8 and IRF2 were compared and contrasted. Subcellular localization analysis showed that CiIRF8 is located both in the cytoplasm and nucleus; however, CiIRF2 is only located in the nucleus. The nuclear-cytoplasmic translocation of CiIRF8 was observed in CIK cells under stimulation with poly(I:C). The interaction of CiIRF8 and CiIRF2 was further confirmed by a co-immunoprecipitation assay in the nucleus. Dual-luciferase reporter assays showed that the promoter activity of Ciifn1 was significantly inhibited by co-transfection with CiIRF2 and CiIRF8. The transcription inhibition of Ciifn1 was alleviated by competitive binding of CiIRF2 and CiIRF8 to CiIRF1. In conclusion, CiIRF8 down-regulates Ciifn1 expression via interaction with CiIRF2 in cells.