Gene Symbol: Irf9
Description: interferon regulatory factor 9
Alias: Irf-9, Isgf3g, p48, interferon regulatory factor 9, IFN-alpha-responsive transcription factor subunit, ISGF-3 gamma, ISGF3 p48 subunit, interferon dependent positive acting transcription factor 3 gamma, interferon-stimulated gene factor 3 gamma, transcriptional regulator ISGF3 subunit gamma
Species: mouse
Products:     Irf9

Top Publications

  1. Wang X, Zhang R, Jiang D, Deng W, Zhang S, Deng S, et al. Interferon regulatory factor 9 protects against hepatic insulin resistance and steatosis in male mice. Hepatology. 2013;58:603-16 pubmed publisher
    ..We found that the expression of interferon (IFN) regulatory factor 9 (IRF9), a major transcription factor mediating IFN responses, was lower in livers of obese mice than in those of their ..
  2. Kimura T, Kadokawa Y, Harada H, Matsumoto M, Sato M, Kashiwazaki Y, et al. Essential and non-redundant roles of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies. Genes Cells. 1996;1:115-24 pubmed
    ..element) which binds a heterotrimeric transcription factor, ISGF3 (IFN-stimulated gene factor 3) consisting of p48 (ISGF3 gamma), Stat1 (Signal transducers and activators of transcription-1; alpha or beta), and Stat2...
  3. Weihua X, Lindner D, Kalvakolanu D. The interferon-inducible murine p48 (ISGF3gamma) gene is regulated by protooncogene c-myc. Proc Natl Acad Sci U S A. 1997;94:7227-32 pubmed
    b>p48 protein is an integral component of the multimeric interferon (IFN)-regulated transcription factor, ISGF3. We have shown earlier that this gene is regulated by a novel IFN-gamma-regulated element...
  4. Sato M, Suemori H, Hata N, Asagiri M, Ogasawara K, Nakao K, et al. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction. Immunity. 2000;13:539-48 pubmed
    ..These results demonstrate the essential and distinct roles of thetwo factors, which together ensure the transcriptional efficiency and diversity of IFN-alpha/beta genes for the antiviral response. ..
  5. Jiang D, Luo Y, Zhang R, Zhang X, Chen H, Zhang Y, et al. Interferon regulatory factor 9 protects against cardiac hypertrophy by targeting myocardin. Hypertension. 2014;63:119-27 pubmed publisher
    Pathological cardiac hypertrophy is a major risk factor for heart failure. In this study, we identified interferon regulatory factor 9 (IRF9), a member of the IRF family, as a previously unidentified negative regulator of cardiac ..
  6. Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, et al. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature. 2005;434:772-7 pubmed
    ..Thus, all elements of IFN responses, whether the systemic production of IFN in innate immunity or the local action of IFN from plasmacytoid dendritic cells in adaptive immunity, are under the control of IRF-7. ..
  7. Thibault D, Chu A, Graham K, Balboni I, Lee L, Kohlmoos C, et al. IRF9 and STAT1 are required for IgG autoantibody production and B cell expression of TLR7 in mice. J Clin Invest. 2008;118:1417-26 pubmed publisher
    ..Here, we demonstrate that 2 IFN-I signaling molecules, IFN regulatory factor 9 (IRF9) and STAT1, were required for the production of IgG autoantibodies in the pristane-induced mouse model of SLE...
  8. Kuriakose T, Man S, Subbarao Malireddi R, Karki R, Kesavardhana S, Place D, et al. ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Sci Immunol. 2016;1:aag2045 pubmed publisher
    ..Overall, these findings indicate that ZBP1 is an innate immune sensor of IAV and highlight its importance in the pathogenesis of IAV infection. ..
  9. Man S, Karki R, Malireddi R, Neale G, Vogel P, Yamamoto M, et al. The transcription factor IRF1 and guanylate-binding proteins target activation of the AIM2 inflammasome by Francisella infection. Nat Immunol. 2015;16:467-75 pubmed publisher
    ..Our results reveal a specific requirement for IRF1 and GBPs in the liberation of DNA for sensing by AIM2 depending on the pathogen encountered by the cell. ..

More Information


  1. Zhang S, Zhu L, Chen H, Zhang R, Zhang P, Jiang D, et al. Interferon regulatory factor 9 is critical for neointima formation following vascular injury. Nat Commun. 2014;5:5160 pubmed publisher
    b>Interferon regulatory factor 9 (IRF9) has various biological functions and regulates cell survival; however, its role in vascular biology has not been explored...
  2. Tang X, Gao J, Guan Y, McLane K, Yuan Z, Ramratnam B, et al. Acetylation-dependent signal transduction for type I interferon receptor. Cell. 2007;131:93-105 pubmed
    ..and phospho-Ser384, CBP acetylates IFNalphaR2 on Lys399, which in turn serves as the docking site for interferon regulatory factor 9 (IRF9)...
  3. Dorner M, Horwitz J, Donovan B, Labitt R, Budell W, Friling T, et al. Completion of the entire hepatitis C virus life cycle in genetically humanized mice. Nature. 2013;501:237-41 pubmed publisher
  4. Marichal T, Ohata K, Bedoret D, Mesnil C, Sabatel C, Kobiyama K, et al. DNA released from dying host cells mediates aluminum adjuvant activity. Nat Med. 2011;17:996-1002 pubmed publisher
  5. Schmid S, Mordstein M, Kochs G, Garcia Sastre A, tenOever B. Transcription factor redundancy ensures induction of the antiviral state. J Biol Chem. 2010;285:42013-22 pubmed publisher
  6. Li W, Hofer M, Jung S, Lim S, Campbell I. IRF7-dependent type I interferon production induces lethal immune-mediated disease in STAT1 knockout mice infected with lymphocytic choriomeningitis virus. J Virol. 2014;88:7578-88 pubmed publisher
    ..infection with lymphocytic choriomeningitis virus (LCMV), STAT1 knockout (KO) mice but not wild-type, STAT2 KO, IRF9 KO, or IFNAR KO mice develop lethal disease perpetrated by CD4(+) T cells...
  7. Thompson C, Hofer M, Campbell I, Holmes A. Community dynamics in the mouse gut microbiota: a possible role for IRF9-regulated genes in community homeostasis. PLoS ONE. 2010;5:e10335 pubmed publisher of BALB/c and C57BL/6 mice and C57BL/6 mice deficient for either type I interferon (IFN) signalling (IRF9 KO mice) or type I and type II IFN signalling (STAT1 KO mice). Temporal variation was found in all mouse strains...
  8. Blaszczyk K, Olejnik A, Nowicka H, Ozgyin L, Chen Y, Chmielewski S, et al. STAT2/IRF9 directs a prolonged ISGF3-like transcriptional response and antiviral activity in the absence of STAT1. Biochem J. 2015;466:511-24 pubmed publisher accumulating for the existence of a signal transducer and activator of transcription 2 (STAT2)/interferon regulatory factor 9 (IRF9)-dependent, STAT1-independent interferon alpha (IFNα) signalling pathway...
  9. Zhang Y, Liu X, She Z, Jiang D, Wan N, Xia H, et al. Interferon regulatory factor 9 is an essential mediator of heart dysfunction and cell death following myocardial ischemia/reperfusion injury. Basic Res Cardiol. 2014;109:434 pubmed publisher
    This study aimed to investigate whether interferon regulatory factor 9 (IRF9) is involved in the pathogenesis of myocardial ischemia-reperfusion (I/R) injury and to explore the underlying molecular mechanisms of this process...
  10. Roy S, Hu J, Meng Q, Hu J, Reddy S, Kalvakolanu D. Development of monoclonal antibodies against GBF1 and their use in studying its functions. J Interferon Cytokine Res. 2005;25:666-73 pubmed
    ..Furthermore, other cytokines, such as interleukin-1 (IL-1) and IL-6, induced the expression of GBF1. These antibodies may be useful tools for investigating the role of GBF1 in cytokine-induced responses. ..
  11. Rauch I, Rosebrock F, Hainzl E, Heider S, Majoros A, Wienerroither S, et al. Noncanonical Effects of IRF9 in Intestinal Inflammation: More than Type I and Type III Interferons. Mol Cell Biol. 2015;35:2332-43 pubmed publisher
    The interferon (IFN)-stimulated gene factor 3 (ISGF3) transcription factor with its Stat1, Stat2, and interferon regulatory factor 9 (IRF9) subunits is employed for transcriptional responses downstream of receptors for type I interferons (..
  12. Abdul Sater A, Majoros A, Plumlee C, Perry S, Gu A, Lee C, et al. Different STAT Transcription Complexes Drive Early and Delayed Responses to Type I IFNs. J Immunol. 2015;195:210-216 pubmed publisher
    ..These observations raise the possibility that this pathway evolved in response to microbes that have devised strategies to subvert Stat1-dependent responses. ..
  13. Suhara W, Yoneyama M, Yonekawa H, Fujita T. Structure of mouse interferon stimulated gene factor 3 gamma (ISGF3 gamma/p48) cDNA and chromosomal localization of the gene. J Biochem. 1996;119:231-4 pubmed
    ..Furthermore, the locus of the ISGF3 gamma gene, designated as Isgf3g, was mapped to distal mouse chromosome 14 by linkage analysis using an intersubspecific backcross typing panel.
  14. Chen H, Guo S, Li Z, Lu Y, Jiang D, Zhang R, et al. A critical role for interferon regulatory factor 9 in cerebral ischemic stroke. J Neurosci. 2014;34:11897-912 pubmed publisher
    ..b>Interferon regulatory factor 9 (IRF9), a transcription factor that regulates innate immune responses, has been implicated in ..
  15. Huber M, Suprunenko T, Ashhurst T, Marbach F, Raifer H, Wolff S, et al. IRF9 Prevents CD8+ T Cell Exhaustion in an Extrinsic Manner during Acute Lymphocytic Choriomeningitis Virus Infection. J Virol. 2017;91: pubmed publisher
    ..The transcription factor interferon regulatory factor 9 (IRF9) is a component of type I interferon (IFN-I) signaling downstream of the IFN-I receptor (IFNAR)...
  16. Lee A, Chen B, Chew M, Barra N, Shenouda M, Nham T, et al. Inflammatory monocytes require type I interferon receptor signaling to activate NK cells via IL-18 during a mucosal viral infection. J Exp Med. 2017;214:1153-1167 pubmed publisher
    ..Mice deficient in type I IFN signaling, Ifnar-/- and Irf9-/- mice, had significantly lower levels of inflammatory monocytes, were deficient in IL-18 ..
  17. Kawakami T, Matsumoto M, Sato M, Harada H, Taniguchi T, Kitagawa M. Possible involvement of the transcription factor ISGF3 gamma in virus-induced expression of the IFN-beta gene. FEBS Lett. 1995;358:225-9 pubmed
    ..These results suggest that ISGF3 gamma or complex containing ISGF3 gamma is involved in the IRF-1-independent pathway mediating IFN-beta gene regulation. ..
  18. Hida S, Ogasawara K, Sato K, Abe M, Takayanagi H, Yokochi T, et al. CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signaling. Immunity. 2000;13:643-55 pubmed
    ..IRF-2 may represent a unique negative regulator, attenuating IFN-alpha/beta-induced gene transcription, which is necessary for balancing the beneficial and harmful effects of IFN-alpha/beta signaling in the immune system. ..
  19. Terawaki S, Chikuma S, Shibayama S, Hayashi T, Yoshida T, Okazaki T, et al. IFN-? directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity. J Immunol. 2011;186:2772-9 pubmed publisher
    ..maintenance of PD-1 expression on TCR-engaged primary mouse T cells through an association IFN-responsive factor 9 (IRF9) to the IFN stimulation response element...
  20. Ousman S, Wang J, Campbell I. Differential regulation of interferon regulatory factor (IRF)-7 and IRF-9 gene expression in the central nervous system during viral infection. J Virol. 2005;79:7514-27 pubmed
  21. Blackburn J, Ohazama A, Kawasaki K, Otsuka Tanaka Y, Liu B, Honda K, et al. The role of Irf6 in tooth epithelial invagination. Dev Biol. 2012;365:61-70 pubmed publisher
    ..Irf6 thus also plays a critical role in regulating epithelial invagination. In addition, we also found that canonical Wnt signaling is upregulated in evaginated incisor epithelium of both Ikk? and Irf6 mutant embryos. ..
  22. Li W, Hofer M, Songkhunawej P, Jung S, Hancock D, Denyer G, et al. Type I interferon-regulated gene expression and signaling in murine mixed glial cells lacking signal transducers and activators of transcription 1 or 2 or interferon regulatory factor 9. J Biol Chem. 2017;292:5845-5859 pubmed publisher
    ..Although IFN-I signal via the interferon-stimulated gene factor 3 (ISGF3) complex consisting of STAT1, STAT2, and IRF9, IFN-I can mediate significant biological effects via ISGF3-independent pathways...
  23. Yiu G, Rasmussen T, Ajami B, Haddon D, Chu A, Tangsombatvisit S, et al. Development of Th17-Associated Interstitial Kidney Inflammation in Lupus-Prone Mice Lacking the Gene Encoding STAT-1. Arthritis Rheumatol. 2016;68:1233-44 pubmed publisher
  24. Yawata M, Murata S, Tanaka K, Ishigatsubo Y, Kasahara M. Nucleotide sequence analysis of the approximately 35-kb segment containing interferon-gamma-inducible mouse proteasome activator genes. Immunogenetics. 2001;53:119-29 pubmed
    ..expressed gene with no known function)-Psme2-Flj10111 (a gene coding for a protein with two RING finger domains)-Isgf3g (an interferon-gamma-inducible gene coding for an interferon-dependent, positive-acting transcription factor 3 ..
  25. Watanabe T, Asano N, Fichtner Feigl S, Gorelick P, Tsuji Y, Matsumoto Y, et al. NOD1 contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the ISGF3 signaling pathway. J Clin Invest. 2010;120:1645-62 pubmed publisher
    ..pylori and possibly other mucosal infections. ..
  26. Hofer M, Li W, Lim S, Campbell I. The type I interferon-alpha mediates a more severe neurological disease in the absence of the canonical signaling molecule interferon regulatory factor 9. J Neurosci. 2010;30:1149-57 pubmed publisher
    ..Interferon regulatory factor (IRF9) is involved in type I IFN-regulated gene expression where it associates with STAT1:STAT2 heterodimers to form the ..
  27. Feng C, Watanabe S, Maruyama S, Suzuki G, Sato M, Furuta T, et al. An alternate pathway for type 1 T cell differentiation. Int Immunol. 1999;11:1185-94 pubmed
    ..This leads to the hypothesis that the IL-12-independent novel pathway for inducing IFN-gamma-producing T cells is distinct from the classical type 1/type 2 T cell subset differentiation pathway. ..
  28. Martinet V, Tonon S, Torres D, Azouz A, Nguyen M, Kohler A, et al. Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8(+) T cells. Nat Commun. 2015;6:7089 pubmed publisher
    ..In conclusion, we demonstrate that type I interferon signalling in CD8(+) T cells drives Eomes expression and thereby regulates the function and homeostasis of memory-like CD8(+) T cells. ..
  29. Hofer M, Li W, Manders P, Terry R, Lim S, King N, et al. Mice deficient in STAT1 but not STAT2 or IRF9 develop a lethal CD4+ T-cell-mediated disease following infection with lymphocytic choriomeningitis virus. J Virol. 2012;86:6932-46 pubmed publisher
    ..While type I IFN signaling is mediated by STAT1, STAT2, and IRF9, type II IFN signaling requires only STAT1...
  30. Kojic S, Nestorovic A, Rakicevic L, Belgrano A, Stankovic M, Divac A, et al. A novel role for cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein. Arch Biochem Biophys. 2010;502:60-7 pubmed publisher
    ..It is probable that Ankrd1/CARP has a role in the propagation of signals initiated by myogenic regulatory factors (MRFs) during myogenesis. ..
  31. McComb S, Cessford E, Alturki N, Joseph J, Shutinoski B, Startek J, et al. Type-I interferon signaling through ISGF3 complex is required for sustained Rip3 activation and necroptosis in macrophages. Proc Natl Acad Sci U S A. 2014;111:E3206-13 pubmed publisher
    ..tonic IFN-stimulated gene factor 3 (ISGF3) signaling, which leads to persistent expression of STAT1, STAT2, and IRF9. Induction of IFNAR1/Rip3-dependent necroptosis also resulted in potent inflammatory pathology in vivo...
  32. Farlik M, Reutterer B, Schindler C, Greten F, Vogl C, Muller M, et al. Nonconventional initiation complex assembly by STAT and NF-kappaB transcription factors regulates nitric oxide synthase expression. Immunity. 2010;33:25-34 pubmed publisher
    ..sequential and cooperative contributions of the transcription factors ISGF3 (a complex containing STAT1, STAT2, and IRF9 subunits) and NF-kappaB to the transcriptional induction of the Nos2 gene in macrophages infected with the ..
  33. Liehl P, Zuzarte Luis V, Chan J, Zillinger T, Baptista F, Carapau D, et al. Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection. Nat Med. 2014;20:47-53 pubmed publisher
    ..Together, our results show that the liver has sensor mechanisms for Plasmodium that mediate a functional antiparasite response driven by type I IFN. ..
  34. Siegfried A, Berchtold S, Manncke B, Deuschle E, Reber J, Ott T, et al. IFIT2 is an effector protein of type I IFN-mediated amplification of lipopolysaccharide (LPS)-induced TNF-? secretion and LPS-induced endotoxin shock. J Immunol. 2013;191:3913-21 pubmed publisher
    ..Thus, IFN-stimulated Ifit2 via enhanced Irf3 phosphorylation upregulates the secretion of proinflammatory cytokines. It thereby amplifies LPS-induced cytokine production and critically influences the outcome of endotoxin shock. ..
  35. Molle C, Goldman M, Goriely S. Critical role of the IFN-stimulated gene factor 3 complex in TLR-mediated IL-27p28 gene expression revealing a two-step activation process. J Immunol. 2010;184:1784-92 pubmed publisher
    ..Type I IFN signaling was necessary for sustained IRF1 activation and formation of the IRF9-containing IFN-stimulated gene factor 3 complex...
  36. Capitini C, Nasholm N, Chien C, Larabee S, Qin H, Song Y, et al. Absence of STAT1 in donor-derived plasmacytoid dendritic cells results in increased STAT3 and attenuates murine GVHD. Blood. 2014;124:1976-86 pubmed publisher
    ..Finally, elevated STAT3 was found in STAT1(-/-) pDCs isolated after alloBMT. We conclude that interfering with interferon signaling in APCs such as pDCs provides a novel approach to regulate the GVHD/GVT axis. ..
  37. Kim S, Koga T, Isobe M, Kern B, Yokochi T, Chin Y, et al. Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation. Genes Dev. 2003;17:1979-91 pubmed
    ..Our study provides a unique example in which a latent transcription factor attenuates the activity of another transcription factor in the cytoplasm, and reveals a new regulatory mechanism in bone remodeling. ..
  38. Begitt A, Droescher M, Meyer T, Schmid C, Baker M, Antunes F, et al. STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling. Nat Immunol. 2014;15:168-76 pubmed publisher
    ..We conclude that STAT1 cooperativity is essential for its biological activity and underlies the cellular responses to type 2, but not type 1 interferon. ..
  39. Wang W, Yin Y, Xu L, Su J, Huang F, Wang Y, et al. Unphosphorylated ISGF3 drives constitutive expression of interferon-stimulated genes to protect against viral infections. Sci Signal. 2017;10: pubmed publisher
    ..that are induced by IFNs through the formation of a tripartite transcription factor ISGF3, which is composed of IRF9 and phosphorylated forms of STAT1 and STAT2...
  40. Farlik M, Rapp B, Marie I, Levy D, Jamieson A, Decker T. Contribution of a TANK-binding kinase 1-interferon (IFN) regulatory factor 7 pathway to IFN-?-induced gene expression. Mol Cell Biol. 2012;32:1032-43 pubmed publisher
    ..Here we show that the Irf7 gene is regulated by transcription factors STAT1 and IRF9 in response to the type II interferon (IFN) IFN-?...
  41. Weihua X, Kolla V, Kalvakolanu D. Interferon gamma-induced transcription of the murine ISGF3gamma (p48) gene is mediated by novel factors. Proc Natl Acad Sci U S A. 1997;94:103-8 pubmed
    In this investigation, we show that the gene encoding p48, a subunit of transcription factor ISGF3, is transcriptionally induced by interferon gamma (IFN-gamma)...