Negative Regulation of Nmi on Virus-Triggered Type I IFN Production by Targeting IRF7

Wang, Jie; Yang, Bo; Hu, Yu; Zheng, Yuhan; Zhou, Haiyan; Wang, Yanming; Ma, Yonglei; Mao, Kairui; Yang, Leilei; Lin, Guomei; Ji, Yongyong; Wu, Xiaodong; Sun, Bing

doi:10.4049/jimmunol.1300740

Cited by 65 publications

(43 citation statements)

References 39 publications

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“…IRF-7 is thought to be a master regulator of type 1 IFN production (33)(34)(35)(36), and induction of IRF-7 mRNA has been reported previously (37) in asthmatic children during periods of respiratory viral infections. As expected, IRF-7 silencing suppressed IFN-a and IFN-b responses.…”

Section: Discussionmentioning

confidence: 93%

CCL7 and IRF-7 Mediate Hallmark Inflammatory and IFN Responses following Rhinovirus 1B Infection

Girkin

Hatchwell

Foster

et al. 2015

The Journal of Immunology

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Rhinovirus infections are common and have the potential to exacerbate asthma. We have determined the lung transcriptome in RV strain 1B (RV1B) infected naïve BALB/c mice (non-allergic) and identified CCL7 and IRF7 amongst the most upregulated mRNA transcripts in the lung. To investigate their roles we employed anti-CCL7 antibodies and an IRF7-targeting small interfering RNA in vivo. Neutralising CCL7 or inhibiting IRF7 limited neutrophil and macrophage influx and IFN responses in non-allergic mice. Neutralising CCL7 also reduced activation of NF-κB p65 and p50 subunits, as well as airways hyperreactivity (AHR) in non-allergic mice. However, neither NF-κB subunit activation nor AHR were abolished with infection of allergic mice after neutralising CCL7, despite a reduction in the number of neutrophils, macrophages and eosinophils. IRF7 siRNA primarily suppressed IFN-α and -β levels during infection of allergic mice. Our data highlight a pivotal role of CCL7 and IRF7 in RV-induced inflammation and IFN responses and link NF-κB signalling to the development of AHR.

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Section: Discussionmentioning

confidence: 93%

CCL7 and IRF-7 Mediate Hallmark Inflammatory and IFN Responses following Rhinovirus 1B Infection

Girkin

Hatchwell

Foster

et al. 2015

The Journal of Immunology

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“…An additional set of genes implicated in antimicrobial responses was identified ( IFIH1, APOBEC3G, C3, CFB, NMI , and IDO1 ). Of these, NMI is noteworthy for its ability to regulate type I IFN responses (51), which block type II IFN (IFN-γ) antimicrobial responses against mycobacterial infection (9). It is interesting that IDO1 (indoleanine 2,3-dioxygenase) is part of this network, indicating that the host is responding as if defending against a tryptophan auxotroph, for example, Leishmania spp., but because M. tuberculosis is a prototroph, it is not effective in killing this pathogen (52).…”

Section: Discussionmentioning

confidence: 99%

IL-32 is a molecular marker of a host defense network in human tuberculosis

et al. 2014

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Tuberculosis is a leading cause of infectious disease–related death worldwide; however, only 10% of people infected with Mycobacterium tuberculosis develop disease. Factors that contribute to protection could prove to be promising targets for M. tuberculosis therapies. Analysis of peripheral blood gene expression profiles of active tuberculosis patients has identified correlates of risk for disease or pathogenesis. We sought to identify potential human candidate markers of host defense by studying gene expression profiles of macrophages, cells that, upon infection by M. tuberculosis, can mount an antimicrobial response. Weighted gene coexpression network analysis revealed an association between the cytokine interleukin-32 (IL-32) and the vitamin D antimicrobial pathway in a network of interferon-γ– and IL-15–induced “defense response” genes. IL-32 induced the vitamin D–dependent antimicrobial peptides cathelicidin and DEFB4 and to generate antimicrobial activity in vitro, dependent on the presence of adequate 25-hydroxyvitamin D. In addition, the IL-15–induced defense response macrophage gene network was integrated with ranked pairwise comparisons of gene expression from five different clinical data sets of latent compared with active tuberculosis or healthy controls and a coexpression network derived from gene expression in patients with tuberculosis undergoing chemotherapy. Together, these analyses identified eight common genes, including IL-32, as molecular markers of latent tuberculosis and the IL-15–induced gene network. As maintaining M. tuberculosis in a latent state and preventing transition to active disease may represent a form of host resistance, these results identify IL-32 as one functional marker and potential correlate of protection against active tuberculosis.

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“…Additionally, several other proteins, for example viral protein R, viral infectivity factor, RBCC protein interacting with PKC1, and caspase-8 have been found to catalyse, maybe not directly promote, the ubiquitination and degradation of IRF3 (Melroe et al, 2007;Okumura et al, 2008;Zhang et al, 2008;Sears et al, 2011). For the regulation of IRF7 degradation, N-Myc and STATs interactor, a negative regulator of the virustriggered type I IFNs, was found to promote K48-linked IRF7 ubiquitination (Wang et al, 2013a). Notably, among those factors responsible for the ubiquitination and degradation of IRFs, Ro52 (TRIM 21) has been highlighted not only for its direct effects on diminishing the transcriptional activities of IRFs, but also for dual functions in their activation (Higgs et al, 2008;.…”

Section: Ubiquitination Of Irfs During Molecular Events Involvingmentioning

confidence: 99%

The interferon regulatory factors as novel potential targets in the treatment of cardiovascular diseases

Zhang

Jiang

2015

British J Pharmacology

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The family of interferon regulatory factors (IRFs) consists of nine members (IRF1-IRF9) in mammals. They act as transcription factors for the interferons and thus exert essential regulatory functions in the immune system and in oncogenesis. Recent clinical and experimental studies have identified critically important roles of the IRFs in cardiovascular diseases, arising from their participation in divergent and overlapping molecular programmes beyond the immune response. Here we review the current knowledge of the regulatory effects and mechanisms of IRFs on the immune system. The role of IRFs and their potential molecular mechanisms as novel stress sensors and mediators of cardiovascular diseases are highlighted. LINKED ARTICLESThis article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi. org/10.1111/bph.2015.172.issue-23 Abbreviations ATF3, activating transcription factor 3; CBP, CREB-binding protein; cDCs, conventional dendritic cells; CLL, chronic lymphocytic leukaemia; CMPs, common myeloid progenitor cells; CREB, cAMP-responsive element-binding protein; Dock2, dedicator of cytokinesis 2; dsRNA, double-stranded RNA; ECM, extracellular matrix; ET-1, endothelin-1; GSK3β, glycogen synthase kinase 3β; GWAS, genome-wide association studies; HATs, histone acetyltransferases; HDACs, histone deacetylases; I/R, ischaemia/reperfusion; IAD, IRF-associated domain; IFN, interferon ; IGF-I, insulin-like growth factor I; iNOS, inducible NOS; IRFs, interferon regulatory factors; MAVS, mitochondrial antiviral signalling protein; MDA5, melanoma differentiation-associated gene 5; MyD88, myeloid differentiation primary-response protein 88; PCAF, p300/CBP-associated factor; pDCs, plasma cytoid dendritic cells; PRR, pattern recognition receptor; RIG-I, retinoic acid-inducible gene I; SLE, systemic lupus erythematosus; SRF, serum response factor; TAD, transcription activation domain; TBK1, TANK-binding kinase 1; TG, transgene; TIRAP, TIR domain-containing adaptor protein; TLRs, Toll-like receptors; TRAF, TNF receptor-associated factor; TRAM, TRIF-related adaptor molecule; TRIF, TIRAP-inducing IFN-β; Tyk2, tyrosine kinase 2; VSMCs, vascular smooth muscle cells Tables of Links Introduction and backgroundThe interferon regulatory factor (IRF) family was first described as transcriptional regulators of the type I interferon (IFN) system. Since 1988, when the first IRF was identified (Miyamoto et al., 1988), most studies of IRFs have focused on their functions in immunity. Abnormalities in IRFs are associated with changes in both innate and adaptive immune responses to cellular and environmental stimuli in a wide variety of pathways. Now, more recent evidence has revealed the remarkable contributions of IRFs to other diseases, such as cardiovascular diseases Jiang et al., 2014d;Zhang et al., 2014a), metabolic diseases (Eguchi et al., 2008;2011; Wang et al., 2013c,d;2014) and oncogenesis (Yanai et al., 2012). In this review, as docume...

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Negative Regulation of Nmi on Virus-Triggered Type I IFN Production by Targeting IRF7

Cited by 65 publications

References 39 publications

CCL7 and IRF-7 Mediate Hallmark Inflammatory and IFN Responses following Rhinovirus 1B Infection

CCL7 and IRF-7 Mediate Hallmark Inflammatory and IFN Responses following Rhinovirus 1B Infection

IL-32 is a molecular marker of a host defense network in human tuberculosis

The interferon regulatory factors as novel potential targets in the treatment of cardiovascular diseases

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