Interferon regulatory factors: Beyond the antiviral response and their link to the development of autoimmune pathology

Anda, Karina Santana-de; Gómez‐Martín, Diana; Díaz-Zamudio, Mariana; Alcocer‐Varela, Jorge

doi:10.1016/j.autrev.2011.08.006

Cited by 40 publications

(15 citation statements)

References 46 publications

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“…IRF5 itself is activated by IFN-α signaling, producing a potential positive feedback loop. In addition to type I IFN [44], IRF5 plays a role in upregulating expression of IL-6, IL-12b, IL-17, IL-23, TNF-α, IFN-β-IP-10, MCP1 and RANTES [45,46] and hence has been called the ‘master regulator of proinflammatory cytokines’ [42,47]. IRF5 has been confirmed as a risk locus for SLE in several different ancestral backgrounds [48–52], and a number of functional genetic variants have been identified.…”

Section: Genetic Variants In Ifn and Ifn-related Pathways Are Associatementioning

confidence: 99%

Genetics of the type I interferon pathway in systemic lupus erythematosus

Ghodke‐Puranik

Niewold

2013

International Journal of Clinical Rheumatology

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Genetic studies of systemic lupus erythematosus (SLE) have been successful, identifying numerous risk factors for human disease. While the list is not yet complete, it is clear that important immune system pathways are represented, one of which being type I interferon (IFN). Circulating type I IFN levels are high in SLE patients and this IFN pathway activation is heritable in families with SLE. We summarize our current understanding of the genetics of the type I IFN pathway in SLE, with an emphasis on studies that demonstrate an impact of the SLE-risk alleles upon type I IFN pathway activation in SLE patients. These studies illustrate that variations in type I IFN pathway genes represent a common genetic feature of SLE. By understanding the genetic regulation of type I IFN, we may be able to intervene in a more personalized fashion, based upon the molecular dysregulation present in a given individual.

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Section: Genetic Variants In Ifn and Ifn-related Pathways Are Associatementioning

confidence: 99%

Genetics of the type I interferon pathway in systemic lupus erythematosus

Ghodke‐Puranik

Niewold

2013

International Journal of Clinical Rheumatology

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“…IRFs are classified into the following four subfamilies: IRF1 (IRF1, 2, and 11), IRF3 (IRF3 and 7), IRF4 (IRF4, 8, 9, and 10), and IRF5 (IRF5 and 6). In certain species, some of these genes are absent, for example, humans and mice lack IRF10 [7] and chickens lack IRF3 and IRF9 [8].…”

Section: Introductionmentioning

confidence: 98%

Molecular characterization and expression analysis of eleven interferon regulatory factors in half-smooth tongue sole, Cynoglossus semilaevis

Zhang

2015

Fish & Shellfish Immunology

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“…Indeed, genetic studies in SLE patients have identified gene variants in pathways connected to Type I IFNs that result in the excessive release of IFNa (30). For example, polymorphisms in IRF5, IRF7 and STAT4, which are part of the signaling pathway of Type I IFNs, are associated with a higher risk of developing SLE (31)(32)(33)(34-36). In animal models, knocking out the genes STAT4 and IRAK-1, which were highlighted by GWAS in SLE patients, decreased disease severity in lupus prone mice (37, 38) and some IFN-related genes, such as Ifi202 (39), are located in susceptibility loci of polygenic lupus prone mice.…”

Section: Introductionmentioning

confidence: 99%

Myeloid Dendritic Cells from B6.NZM Sle1/Sle2/Sle3 Lupus-Prone Mice Express an IFN Signature That Precedes Disease Onset

Sriram

Varghese

Bennett

et al. 2012

The Journal of Immunology

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Patients with systemic lupus erythematosus (SLE) show an over-expression of Type I Interferon (IFN) responsive genes called “Interferon Signature”. We found that the B6.NZMSle1/Sle2/Sle3 (Sle1,2,3) lupus-prone mice also express an Interferon Signature compared to non autoimmune C57BL/6 mice. In vitro, myeloid dendritic cells (mDCs)(GM-CSF bone marrow-derived BMDCs) from Sle1,2,3 mice constitutively over-expressed IFN responsive genes such as IFNb, Oas-3, Mx-1, ISG-15 and CXCL10, and the members of IFN signaling pathway STAT1, STAT2, and IRF7. The Interferon Signature was similar in Sle1,2,3 BMDCs from young, pre-autoimmune mice and from mice with high titers of autoantibodies, suggesting that the Interferon Signature in mDCs precedes disease onset and it is independent from the autoantibodies. Sle1,2,3 BMDCs hyper-responded to stimulation with IFNa and the TLR7 and TLR9 agonists R848 and CpGs. We propose that this hyper-response is induced by the Interferon Signature and only partially contributes to the Signature, since oligonucleotides inhibitory for TLR7 and TLR9 only partially suppressed the constitutive Interferon Signature and pre-exposure to IFNa induced the same hyper-response in wild type BMDCs than in Sle1,2,3 BMDCs. In vivo, mDCs and with lesser extent T and B cells from young pre-diseased Sle1,2,3 mice also expressed the Interferon Signature, although they lacked the strength that BMDCs showed in vitro. Sle1,2,3 plasmacytoid DCs expressed the Interferon Signature in vitro but not in vivo, suggesting that mDCs may be more relevant before disease onset. We propose that Sle1,2,3 mice are useful tools to study the role of the Interferon Signature in lupus pathogenesis.

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Interferon regulatory factors: Beyond the antiviral response and their link to the development of autoimmune pathology

Cited by 40 publications

References 46 publications

Genetics of the type I interferon pathway in systemic lupus erythematosus

Genetics of the type I interferon pathway in systemic lupus erythematosus

Molecular characterization and expression analysis of eleven interferon regulatory factors in half-smooth tongue sole, Cynoglossus semilaevis

Myeloid Dendritic Cells from B6.NZM Sle1/Sle2/Sle3 Lupus-Prone Mice Express an IFN Signature That Precedes Disease Onset

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