Genomes and Genes
interferon regulatory factors
Summary: A family of transcription factors that share an N-terminal HELIX-TURN-HELIX MOTIF and bind INTERFERON-inducible promoters to control GENE expression. IRF proteins bind specific DNA sequences such as interferon-stimulated response elements, interferon regulatory elements, and the interferon consensus sequence.
- Man K, Miasari M, Shi W, Xin A, Henstridge D, Preston S, et al. The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells. Nat Immunol. 2013;14:1155-65 pubmed publisher..Thus, IRF4 is an indispensable molecular 'rheostat' that 'translates' TCR affinity into the appropriate transcriptional programs that link metabolic function with the clonal selection and effector differentiation of T cells. ..
- Negishi H, Yanai H, Nakajima A, Koshiba R, Atarashi K, Matsuda A, et al. Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Nat Immunol. 2012;13:659-66 pubmed publisher..The innate immune receptor cross-interference we describe may have implications for infection-associated clinical episodes. ..
- Niewold T, Kelly J, Kariuki S, Franek B, Kumar A, Kaufman K, et al. IRF5 haplotypes demonstrate diverse serological associations which predict serum interferon alpha activity and explain the majority of the genetic association with systemic lupus erythematosus. Ann Rheum Dis. 2012;71:463-8 pubmed publisher..immune complexes which can stimulate IFN? production by activating endosomal Toll-like receptors and interferon regulatory factors (IRFs), including IRF5...
- Li P, Spolski R, Liao W, Wang L, Murphy T, Murphy K, et al. BATF-JUN is critical for IRF4-mediated transcription in T cells. Nature. 2012;490:543-6 pubmed publisher..These findings reveal that IRF4 can signal via complexes containing ETS or AP1 motifs depending on the cellular context, thus indicating new approaches for modulating IRF4-dependent transcription. ..
- Masuda T, Tsuda M, Yoshinaga R, Tozaki Saitoh H, Ozato K, Tamura T, et al. IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype. Cell Rep. 2012;1:334-340 pubmed publisher..Therefore, IRF8 may activate a program of gene expression that transforms microglia into a reactive phenotype. Our findings provide a newly observed mechanism for microglial activation. ..
- Salahshourifar I, Wan Sulaiman W, Halim A, Zilfalil B. Mutation screening of IRF6 among families with non-syndromic oral clefts and identification of two novel variants: review of the literature. Eur J Med Genet. 2012;55:389-93 pubmed publisher..While, IRF6 variants could, at best, contribute to clefting as part of a complex inheritance pattern, with both additional genes and environmental factors having a role. ..
- Lech M, Weidenbusch M, Kulkarni O, Ryu M, Darisipudi M, Susanti H, et al. IRF4 deficiency abrogates lupus nephritis despite enhancing systemic cytokine production. J Am Soc Nephrol. 2011;22:1443-52 pubmed publisher..Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells. ..
- Marquis J, Kapoustina O, Langlais D, Ruddy R, Dufour C, Kim B, et al. Interferon regulatory factor 8 regulates pathways for antigen presentation in myeloid cells and during tuberculosis. PLoS Genet. 2011;7:e1002097 pubmed publisher..These results identify IRF8 as a key regulator of early response pathways in myeloid cells, including phagosome maturation, antigen processing, and antigen presentation by myeloid cells. ..
- Fang C, Roy S, Nielsen E, Paul M, Maul R, Paun A, et al. Unique contribution of IRF-5-Ikaros axis to the B-cell IgG2a response. Genes Immun. 2012;13:421-30 pubmed publisher..We show that IRF-8 but not IRF-4 activates the ikzf1 promoter, and IRF-5 inhibits the transcriptional activity of IRF-8. Collectively, these results identify the IRF-5-Ikaros axis as a critical modulator of IgG2a/c class switching. ..
- Ciofani M, Madar A, Galan C, Sellars M, Mace K, Pauli F, et al. A validated regulatory network for Th17 cell specification. Cell. 2012;151:289-303 pubmed publisher..This interconnected network can be used to investigate new therapeutic approaches to manipulate Th17 functions in the setting of inflammatory disease. ..
- Josset L, Belser J, Pantin Jackwood M, Chang J, Chang S, Belisle S, et al. Implication of inflammatory macrophages, nuclear receptors, and interferon regulatory factors in increased virulence of pandemic 2009 H1N1 influenza A virus after host adaptation. J Virol. 2012;86:7192-206 pubmed publisher..i) an early and sustained inflammatory and interferon response that could be driven in part by interferon regulatory factors (IRFs) and increased NF-?B activation, as well as inhibition of the negative regulator TRIM24, (ii) ..
- Bajana S, Roach K, Turner S, Paul J, Kovats S. IRF4 promotes cutaneous dendritic cell migration to lymph nodes during homeostasis and inflammation. J Immunol. 2012;189:3368-77 pubmed..Thus, although dispensable for their development, IRF4 is crucial for the CCR7-mediated migration of CD11b(+) dDC, a predominant population in murine and human skin that plays a vital role in normal and pathogenic cutaneous immunity. ..
- Letra A, Fakhouri W, Fonseca R, Menezes R, Kempa I, Prasad J, et al. Interaction between IRF6 and TGFA genes contribute to the risk of nonsyndromic cleft lip/palate. PLoS ONE. 2012;7:e45441 pubmed publisher..Moreover, this potential IRF6-TGFA interaction may account for as much as 1% to 10% of CL/P cases. The Irf6-knockout model further supports the evidence of IRF6-TGFA interaction found in humans. ..
- Havelange V, Pekarsky Y, Nakamura T, Palamarchuk A, Alder H, Rassenti L, et al. IRF4 mutations in chronic lymphocytic leukemia. Blood. 2011;118:2827-9 pubmed publisher..5%). Patients with IRF4 mutation have a good prognosis, and 4 of 6 have a trisomy 12. We also found that IRF4 mRNA expression is higher in the patients with the mutation. ..
- Sweeney S. Targeting interferon regulatory factors to inhibit activation of the type I IFN response: implications for treatment of autoimmune disorders. Cell Immunol. 2011;271:342-9 pubmed publisher..IRF regulation of inflammation and induction of the IFN signature might contribute to the pathogenesis of autoimmune diseases and therefore represent novel therapeutic targets. ..
- Biggs L, Rhea L, Schutte B, Dunnwald M. Interferon regulatory factor 6 is necessary, but not sufficient, for keratinocyte differentiation. J Invest Dermatol. 2012;132:50-8 pubmed publisher..7? kb upstream of the Irf6 start site, we demonstrated that this element contributes to the regulation of Irf6 in the epidermis and keratinocytes in culture. ..
- Shin D, Lee C, Morse H. IRF8 governs expression of genes involved in innate and adaptive immunity in human and mouse germinal center B cells. PLoS ONE. 2011;6:e27384 pubmed publisher..We also showed that IRF8 target genes contributes to multiple aspects of the biology of mature B cells including critical components of the molecular crosstalk among GC B cells, T follicular helper cells, and follicular dendritic cells...
- Cherian T, Kariuki S, Franek B, Buyon J, Clancy R, Niewold T. Brief Report: IRF5 systemic lupus erythematosus risk haplotype is associated with asymptomatic serologic autoimmunity and progression to clinical autoimmunity in mothers of children with neonatal lupus. Arthritis Rheum. 2012;64:3383-7 pubmed publisher..SS in mothers of children with NL was associated with different IRF5 haplotypes. These data suggest that IRF5 polymorphisms play a role in serologic autoimmunity in humans and may promote the progression to clinical autoimmunity. ..
- Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol. 2011;11:750-61 pubmed publisher..In this Review, we summarize the current knowledge of transcriptional and chromatin-mediated control of macrophage polarization in physiology and disease. ..
- Santana de Anda K, Gómez Martín D, Díaz Zamudio M, Alcocer Varela J. Interferon regulatory factors: beyond the antiviral response and their link to the development of autoimmune pathology. Autoimmun Rev. 2011;11:98-103 pubmed publisher..Among these, are the interferon regulatory factors (IRF)...
- Sharif R, Mayes M, Tan F, Gorlova O, Hummers L, Shah A, et al. IRF5 polymorphism predicts prognosis in patients with systemic sclerosis. Ann Rheum Dis. 2012;71:1197-202 pubmed publisher..An SNP in the IRF5 promoter region (rs4728142), associated with lower IRF5 transcript levels, was predictive of longer survival and milder ILD in patients with SSc. ..
- ..These remarkably proficient proteins also provide noncanonical functions in transcriptional regulation and they also function in mitochondrial respiration and chromatin organization in ways that may not involve transcription at all. ..
- Lichtman E, Helfgott S, Kriegel M. Emerging therapies for systemic lupus erythematosus--focus on targeting interferon-alpha. Clin Immunol. 2012;143:210-21 pubmed publisher..These include monoclonal antibodies against IFN?, anti-IFN? antibody-inducing vaccines, and inhibitors of Toll-like receptors. We also summarize the current status of these pharmaceutical agents in early clinical trials. ..
- Hart K, Kimura S, Mushailov V, Budimlija Z, Prinz M, Wurmbach E. Improved eye- and skin-color prediction based on 8 SNPs. Croat Med J. 2013;54:248-56 pubmed..We can conclude that the new 8-plex system for the prediction of eye and skin color substantially enhances its former version. ..
- Jacobs S, Gregory S, West J, Wollish A, Bennett C, Blackbourn D, et al. The viral interferon regulatory factors of kaposi's sarcoma-associated herpesvirus differ in their inhibition of interferon activation mediated by toll-like receptor 3. J Virol. 2013;87:798-806 pubmed publisher..Altogether, this report indicates that vIRFs are able to block IFN mediated by TLRs but that each vIRF has a unique function and mechanism for blocking antiviral IFN responses...
- Stone R, Feng D, Deng J, Singh S, Yang L, Fitzgerald Bocarsly P, et al. Interferon regulatory factor 5 activation in monocytes of systemic lupus erythematosus patients is triggered by circulating autoantigens independent of type I interferons. Arthritis Rheum. 2012;64:788-98 pubmed publisher..This study provides the first formal proof that IRF-5 activation is altered in the monocytes of SLE patients, which can be attributed, in part, to the SLE blood environment. ..
- Cunninghame Graham D, Morris D, Bhangale T, Criswell L, Syvanen A, Rönnblom L, et al. Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus. PLoS Genet. 2011;7:e1002341 pubmed publisher..These results increase the number of established susceptibility genes for lupus to ~30 and validate the importance of using large datasets to confirm associations of loci which moderately increase the risk for disease. ..
- Becker A, Michael D, Satpathy A, Sciammas R, Singh H, Bhattacharya D. IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors. Blood. 2012;119:2003-12 pubmed publisher..These data suggest that IRF-8 represses a neutrophil module of development and promotes convergent DC development from multiple lymphoid and myeloid progenitors autonomously of cellular context. ..
- Goswami R, Jabeen R, Yagi R, Pham D, Zhu J, Goenka S, et al. STAT6-dependent regulation of Th9 development. J Immunol. 2012;188:968-75 pubmed publisher..These data established a transcription factor network that regulates IL-9 and demonstrated how combinations of cytokine signals generate cytokine-secreting potential by altering the expression of a panel of transcription factors. ..
- Yang J, Hu X, Zimmerman M, Torres C, Yang D, Smith S, et al. Cutting edge: IRF8 regulates Bax transcription in vivo in primary myeloid cells. J Immunol. 2011;187:4426-30 pubmed publisher..Our findings show that IRF8 directly regulates Bax transcription in vivo, but not in vitro during myeloid cell lineage differentiation. ..
- Järvinen T, Hellquist A, Zucchelli M, Koskenmies S, Panelius J, Hasan T, et al. Replication of GWAS-identified systemic lupus erythematosus susceptibility genes affirms B-cell receptor pathway signalling and strengthens the role of IRF5 in disease susceptibility in a Northern European population. Rheumatology (Oxford). 2012;51:87-92 pubmed publisher..Our results attest the importance of B-cell receptor pathway and IFN signalling in SLE pathogenesis. ..
- Glasmacher E, Agrawal S, Chang A, Murphy T, Zeng W, Vander Lugt B, et al. A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science. 2012;338:975-80 pubmed publisher..This genomic regulatory element and cognate factors appear to have evolved to integrate diverse immunomodulatory signals. ..
- Chopin M, Chacón Martínez C, Jessberger R. Fine tuning of IRF-4 expression by SWAP-70 controls the initiation of plasma cell development. Eur J Immunol. 2011;41:3063-74 pubmed publisher..Thus, in a dose-dependent manner, SWAP-70 controls IRF-4 protein expression and thereby regulates the initiation of PC differentiation...
- Tussiwand R, Lee W, Murphy T, Mashayekhi M, Kc W, Albring J, et al. Compensatory dendritic cell development mediated by BATF-IRF interactions. Nature. 2012;490:502-7 pubmed publisher..Conceivably, manipulating this alternative pathway of dendritic cell development could be of value in augmenting immune responses to vaccines. ..
- Wang L, Toomey N, Diaz L, Walker G, Ramos J, Barber G, et al. Oncogenic IRFs provide a survival advantage for Epstein-Barr virus- or human T-cell leukemia virus type 1-transformed cells through induction of BIC expression. J Virol. 2011;85:8328-37 pubmed publisher..Our findings have identified Bic as the first miRNA-encoding gene for IRFs and provide evidence for a novel molecular mechanism underlying the IRF/BIC pathway in viral oncogenesis. ..
- Yao S, Buzo B, Pham D, Jiang L, Taparowsky E, Kaplan M, et al. Interferon regulatory factor 4 sustains CD8(+) T cell expansion and effector differentiation. Immunity. 2013;39:833-45 pubmed publisher..Our data reveal that IRF4 translates differential strength of TCR signaling into different quantitative and qualitative CD8(+) T cell responses. ..
- Martin J, Broen J, Carmona F, Teruel M, Simeon C, Vonk M, et al. Identification of CSK as a systemic sclerosis genetic risk factor through Genome Wide Association Study follow-up. Hum Mol Genet. 2012;21:2825-35 pubmed publisher..This study significantly increases the number of known putative genetic risk factors for SSc, including the genes CSK, PSD3 and NFKB1, and further confirms six previously described ones. ..
- Nordang G, Viken M, Amundsen S, Sanchez E, Flatø B, Førre O, et al. Interferon regulatory factor 5 gene polymorphism confers risk to several rheumatic diseases and correlates with expression of alternative thymic transcripts. Rheumatology (Oxford). 2012;51:619-26 pubmed publisher..The IFN pathway gene, IRF5, is a common susceptibility factor for several rheumatic and autoimmune diseases, and risk variants are correlated with expression of alternative IRF5 transcripts in thymus implying a regulatory role. ..
- Elding H, Lau W, Swallow D, Maniatis N. Dissecting the genetics of complex inheritance: linkage disequilibrium mapping provides insight into Crohn disease. Am J Hum Genet. 2011;89:798-805 pubmed publisher..The application of this method thus paves the way for understanding complex inheritance in general, leading to the dissection of different pathways and ultimately, personalized treatment. ..
- Botti E, Spallone G, Moretti F, Marinari B, Pinetti V, Galanti S, et al. Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas. Proc Natl Acad Sci U S A. 2011;108:13710-5 pubmed publisher..These results indicate a function for IRF6 in suppression of tumorigenesis in stratified epithelia. ..
- Leslie E, Mansilla M, Biggs L, Schuette K, Bullard S, Cooper M, et al. Expression and mutation analyses implicate ARHGAP29 as the etiologic gene for the cleft lip with or without cleft palate locus identified by genome-wide association on chromosome 1p22. Birth Defects Res A Clin Mol Teratol. 2012;94:934-42 pubmed publisher..This work suggests a novel pathway in which the IRF6 gene regulatory network interacts with the Rho pathway via ARHGAP29. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc. ..
- Robinson B, Estep R, Messaoudi I, Rogers K, Wong S. Viral interferon regulatory factors decrease the induction of type I and type II interferon during rhesus macaque rhadinovirus infection. J Virol. 2012;86:2197-211 pubmed publisher..two closely related gammaherpesviruses, are unique in their expression of viral homologs of cellular interferon regulatory factors (IRFs), termed viral IRFs (vIRFs)...
- Shukla V, Ma S, Hardy R, Joshi S, Lu R. A role for IRF4 in the development of CLL. Blood. 2013;122:2848-55 pubmed publisher..Moreover, our findings establish IRF4(-/-)Vh11 mice as a novel mouse model of CLL that not only is valuable for dissecting molecular pathogenesis of CLL but could also be used for therapeutic purposes. ..
- Larrabee Y, Birkeland A, Kent D, Flores C, Su G, Lee J, et al. Association of common variants, not rare mutations, in IRF6 with nonsyndromic clefts in a Honduran population. Laryngoscope. 2011;121:1756-9 pubmed publisher..rs642961 has been previously reported to have an effect in other populations, suggesting that different populations may be affected by different polymorphisms. ..
- Brito L, Bassi C, Masotti C, Malcher C, Rocha K, Schlesinger D, et al. IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population. Am J Med Genet A. 2012;158A:2170-5 pubmed publisher..We did not find any correlation between expression levels and genotypes of the two loci, and it is possible that these SNPs have a functional role in some specific period of embryogenesis. ..
- Ochiai K, Maienschein Cline M, Simonetti G, Chen J, Rosenthal R, Brink R, et al. Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4. Immunity. 2013;38:918-29 pubmed publisher..Our results support a model of "kinetic control" in which signaling-induced dynamics of IRF4 in activated B cells control their cell-fate outcomes...
- Courties G, Heidt T, Sebas M, Iwamoto Y, Jeon D, Truelove J, et al. In vivo silencing of the transcription factor IRF5 reprograms the macrophage phenotype and improves infarct healing. J Am Coll Cardiol. 2014;63:1556-66 pubmed publisher..05). This work identified a new therapeutic avenue to augment resolution of inflammation in healing infarcts by macrophage phenotype manipulation. This therapeutic concept may be used to attenuate post-MI remodeling and heart failure. ..