The IRF family, revisited

Abstract

Since the discovery of interferon 50 years ago a great deal of progress has been made in understanding how interferons work and how and why they are induced. Key factors in interferon induction are the interferon regulatory factors (IRF). In this review of IRF we aim to show you not only the historical side of the IRF but also the integral, anti-viral and hematopoetic roles of these transcription factors, as well as the sometimes surprising and even forgotten roles that these proteins play, not only in interferon signaling but throughout the immune system and the body as a whole. Further research will no doubt expand the repertoire of these multifunctional proteins even more.

Fish IRF6 is a positive regulator of IFN expression and involved in both of the MyD88 and TBK1 pathways

“…Fish homologs are also crucial for IFN regulation as transcription factors, for Most IRFs, containing an N-terminal DNA binding domain (DBD) and a C-terminal IRF association domain (IAD), mediating interaction with target gene promoters and association with other proteins, respectively [19,20]. Divided by the capacity of IFN regulation, zebrafish IRF1, IRF3, IRF4, IRF5, IRF7, IRF8, IRF9 and IRF11 are the positive regulators, and IRF2 and IRF10 play the negative roles [21e25].…”

Types I and II interferons upregulate the costimulatory CD80 molecule in monocytes via interferon regulatory factor-1

“…Type I and type II IFNs, by respectively binding type I and type II IFN-receptors, activate both similar 4 and dissimilar Jak/Stat signal pathways [18][19][20]. IFN-- stimulation leads to the formation of two transcriptional activator complexes, a homodimer of signal transducer and activator of transcription (Stat)1 and IFN-stimulated gene factor 3 (ISGF3) which comprises Stat1, Stat2 and IRF-9 (or p48) [21]. Stat1 homodimer binds IFN--activated site (GAS) motifs in promoter regions of various genes, such as interferon regulatory factor-1 (IRF-1) gene [20,21].…”

“…IFN-- stimulation leads to the formation of two transcriptional activator complexes, a homodimer of signal transducer and activator of transcription (Stat)1 and IFN-stimulated gene factor 3 (ISGF3) which comprises Stat1, Stat2 and IRF-9 (or p48) [21]. Stat1 homodimer binds IFN--activated site (GAS) motifs in promoter regions of various genes, such as interferon regulatory factor-1 (IRF-1) gene [20,21]. ISGF3 binds to IFN-stimulated response element (ISRE) promoter regions in ISREcontaining genes, including IRF-7 gene, and activates their transcription [21].…”

“…Stat1 homodimer binds IFN--activated site (GAS) motifs in promoter regions of various genes, such as interferon regulatory factor-1 (IRF-1) gene [20,21]. ISGF3 binds to IFN-stimulated response element (ISRE) promoter regions in ISREcontaining genes, including IRF-7 gene, and activates their transcription [21]. IFN- signals mainly through Stat1 homodimer [20,21].…”

“…ISGF3 binds to IFN-stimulated response element (ISRE) promoter regions in ISREcontaining genes, including IRF-7 gene, and activates their transcription [21]. IFN- signals mainly through Stat1 homodimer [20,21]. In addition, IFN- and IFN- may exhibit separate bioactivities through their different affinities and rate constants of interaction with IFN type I receptor subunits [22,23].…”