Protein interaction for an interferon-inducible systemic lupus associated gene, IFIT1

Ye, Sheng; Hua, Peng; Gu, Yiren; Hua, Jing; Chen, X.-G.; Bao, Chunde; Wang, Y.; Zhang, W.; Jiang, Qian; Tsao, Betty P.; Hahn, BH; Chen, S.-L.; Rao, Zhongchen; Shen, Nan

doi:10.1093/rheumatology/keg315

Cited by 72 publications

(56 citation statements)

References 20 publications

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“…G1P2 has also been demonstrated to enhance the innate antiviral response via regulation of IFN-stimulated intracellular signaling pathways (64). Notably, for other genes including IFIT1, IFIT4, and IFI44, there is limited knowledge regarding their biochemical function or biological effect for the host, although it has been noted that their expression is increased in the autoimmune disease systemic lupus erythematosus (65,66). It is therefore interesting to speculate that periodontitis could exhibit an autoimmune component that may result from inefficient tissue autophagy (67).…”

Section: Discussionmentioning

confidence: 99%

Periodontitis Associates with a Type 1 IFN Signature in Peripheral Blood Neutrophils

Wright

Matthews

Chapple

et al. 2008

The Journal of Immunology

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Peripheral blood neutrophils from periodontitis patients exhibit a hyperreactive and hyperactive phenotype (collectively termed hyperresponsivity) in terms of production of reactive oxygen species (ROS). The molecular basis for this phenomenon, however, has yet to be determined. Our objectives were to identify genes differentially expressed in hyperresponsive peripheral blood neutrophils from chronic periodontitis patients relative to periodontally healthy controls and use these data to identify potential contributory pathways to the hyperresponsive neutrophil phenotype. Using microarray technology we demonstrated differential expression of 163 genes (149 increased, 14 decreased) representing a range of ontological classes. There was increased expression of a significant number of IFN-stimulated genes (ISG). RT-PCR analysis of ISG transcripts in individual and pooled samples further corroborated these data, and indicated that levels decreased to near those of controls following successful therapy. Significantly enhanced FcγR-stimulated ROS production was subsequently achieved by priming control neutrophils with IFN-α/-β/-γ, but not LPS, and gene expression analysis indicated that exposure to the type I IFN (in particular IFN-α) better replicated the mRNA profile observed in vivo. Further studies demonstrated that plasma levels of IFN-α were significantly higher in samples from patients relative to unaffected controls. Following successful periodontitis treatment, plasma IFN-α levels, neutrophil ISG expression, and FcγR-stimulated neutrophil ROS output of patients, all decreased to levels comparable with those of controls. In conclusion, although chronic periodontitis is a complex disease, raised IFN-α may be one determinant of the distinct molecular phenotype and hyperresponsivity exhibited by patients’ peripheral blood neutrophils.

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Section: Discussionmentioning

confidence: 99%

Periodontitis Associates with a Type 1 IFN Signature in Peripheral Blood Neutrophils

Wright

Matthews

Chapple

et al. 2008

The Journal of Immunology

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“…Comprehensive profiling of gene expression in peripheral blood mononuclear cells (PBMCs) and protein expression in sera from patients has consistently shown the upregulation of IFN-inducible genes in SLE compared with normal controls. 10,11,13,[49][50][51][52] IFN signature in PBMCs Baechler et al 10 studied gene expression microarray profiles in 48 SLE patients and 42 controls to identify pathways that might be dysregulated in PBMCs of SLE patients. Several immune-related genes were up-regulated in the SLE patients including Fc receptor for IgA (FCAR, CD89), Fc receptor for IgG such as FcgRIIA (CD32) and FcgRI (CD64), TNFRSF6 (Fas/CD95), and three molecules in the inflammatory IL-1 cytokine pathway: IL-1b, IL-1 receptor II (IL-1RII) and IL-1 receptor antagonist.…”

Section: Expression Profiling Of Ifn-responsive Genes In Slementioning

confidence: 99%

“…53 Among these, at least nine genes (LY6E, OASL, IFIT1, IFIT4, STAT1, MX1, MX2, PLSCR1 and IRF7) were replicated by other independently carried out microarray studies. 11,[49][50][51] Baechler and co-workers 10,53 also examined whether there was any clinical feature that distinguishes 'IFNhigh' group of patients from 'IFN-low group'. The frequency of SLE who have a manifestation of renal disease, central nervous system lupus and hematological deficit (particularly leukopenia, lymphopenia and thrombocytopenia) was significantly higher in the 'IFNhigh' group of patients as compared to the 'IFN-low', suggesting that IFN signature can be a marker for patients with severe SLE.…”

Section: Expression Profiling Of Ifn-responsive Genes In Slementioning

confidence: 99%

A compass that points to lupus: genetic studies on type I interferon pathway

Kyogoku

Tsuchiya

2007

Genes Immun

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It was more than 20 years ago that patients with systemic lupus erythematosus (SLE) were first reported to display elevated serum levels of type I interferon (IFN). Since then, extensive studies revealed a crucial role for type I IFN in SLE pathogenesis. The current model proposes that small increase of type I IFN production by plasmacytoid dendritic cells (pDCs) is sufficient to induce unabated activation of immature peripheral DCs. IFN-matured DCs select and activate autoreactive T cells and B cells, rather than deleting them, resulting in peripheral tolerance breakdown, a characteristic feature of SLE. Furthermore, immune complexes provide an amplification loop to pDCs for further IFN production. In the past 5 years, high-throughput technologies such as expression profiling and single-nucleotide polymorphism (SNP) typing established the role of altered type I IFN system in SLE, and a detailed picture of its molecular mechanisms is beginning to emerge. In this review, we discuss two major lines of genetics studies on type I IFN pathway related to human SLE: (1) expression profiling of IFN-responsive genes and (2) disease-associated SNPs of IFN-related genes, especially IRF5 (IFN-regulatory factor 5). Lastly, we discuss how such genetic alterations in type I IFN pathway fit in the current model of SLE pathogenesis.

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“…Recently, OAS was rediscovered to be a part of interferon signature(s), which plays an important role in the pathogenesis of SLE by several microarray gene expression studies [47] , [48]. These studies have identified three isoforms of OAS, i.e., OAS1, OAS2, and OASL.…”

Section: ′5′-oligoadenylate Synthetasementioning

confidence: 99%

Systemic lupus erythematosus and infections: Clinical importance of conventional and upcoming biomarkers

Sciascia

Ceberio

Garcia-Fernandez

et al. 2012

Autoimmunity Reviews

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Protein interaction for an interferon-inducible systemic lupus associated gene, IFIT1

Cited by 72 publications

References 20 publications

Periodontitis Associates with a Type 1 IFN Signature in Peripheral Blood Neutrophils

Periodontitis Associates with a Type 1 IFN Signature in Peripheral Blood Neutrophils

A compass that points to lupus: genetic studies on type I interferon pathway

Systemic lupus erythematosus and infections: Clinical importance of conventional and upcoming biomarkers

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