Abstract 4141: Role of interferon regulatory factor 5 in anti-tumor immunity: Orchestration of a functional tertiary lymphoid structure

2016 ◽  
Author(s):  
Erica Pimenta ◽  
Ryan Weiss ◽  
Dan Li ◽  
Betsy Barnes
Keyword(s):  
Tumor Immunity ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5

scholarly journals Interferon Regulatory Factor 5 in the Pathogenesis of Systemic Lupus Erythematosus

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Candace M. Cham ◽  
Kichul Ko ◽  
Timothy B. Niewold
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Interferon Regulatory Factor ◽  
Immune Defense ◽  
Toll Like Receptors ◽  
Regulatory Factor ◽  
Systemic Lupus ◽  
Interferon Regulatory Factor 5

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple genetic risk factors, high levels of interferon alpha (IFN-α), and the production of autoantibodies against components of the cell nucleus. Interferon regulatory factor 5 (IRF5) is a transcription factor which induces the transcription of IFN-αand other cytokines, and genetic variants of IRF5 have been strongly linked to SLE pathogenesis. IRF5 functions downstream of Toll-like receptors and other microbial pattern-recognition receptors, and immune complexes made up of SLE-associated autoantibodies seem to function as a chronic endogenous stimulus to this pathway. In this paper, we discuss the physiologic role of IRF5 in immune defense and the ways in whichIRF5variants may contribute to the pathogenesis of human SLE. Recent data regarding the role ofIRF5in both serologic autoimmunity and the overproduction of IFN-αin human SLE are summarized. These data support a model in which SLE-risk variants of IRF5 participate in a “feed-forward” mechanism, predisposing to SLE-associated autoantibody formation, and subsequently facilitating IFN-αproduction downstream of Toll-like receptors stimulated by immune complexes composed of these autoantibodies.

scholarly journals Functional Regulation of MyD88-Activated Interferon Regulatory Factor 5 by K63-Linked Polyubiquitination

2008 ◽  
Vol 28 (24) ◽  
pp. 7296-7308 ◽  
Author(s):  
Mumtaz Yaseen Balkhi ◽  
Katherine A. Fitzgerald ◽  
Paula M. Pitha
Keyword(s):  
Nuclear Translocation ◽  
Interferon Regulatory Factor ◽  
Type I Interferons ◽  
Type I ◽  
Regulatory Factor ◽  
Induction Program ◽  
Interferon Regulatory Factor 5 ◽  
Lysine Residues ◽  
Functional Regulation

ABSTRACT Interferon regulatory factor 5 (IRF-5) plays an important role in the innate antiviral and inflammatory response. Specific IRF-5 haplotypes are associated with dysregulated expression of type I interferons and predisposition to autoimmune disorders. IRF-5 is activated by Toll-like receptor 7 (TLR7) and TLR9 via the MyD88 pathway, where it interacts with both MyD88 and the E3 ubiquitin ligase, TRAF6. To understand the role of these interactions in the regulation of IRF-5, we examined the role of ubiquitination and showed that IRF-5 is subjected to TRAF6-mediated K63-linked ubiquitination, which is important for IRF-5 nuclear translocation and target gene regulation. We show that while the murine IRF-5 and human IRF-5 variant 4 (HuIRF-5v4) and HuIRF-5v5 are ubiquitinated, an IRF-5 bone marrow variant mutant containing an internal deletion of 288 nucleotides is not ubiquitinated. Lysine residues at positions 410 and 411 in a putative TRAF6 consensus binding domain of IRF-5 are the targets of K63-linked ubiquitination. Mutagenesis of these two lysines abolished IRF-5 ubiquitination, nuclear translocation, and the IFNA promoter-inducing activity but not the IRF-5-TRAF6 interaction. Finally, we show that IRAK1 associates with IRF-5 and that this interaction precedes and is required for IRF-5 ubiquitination and activation. Thus, our findings offer a new mechanistic insight into IRF-5 gene induction program through hitherto unknown processes of IRF-5 ubiquitination.

The Role of Interferon Regulatory Factor 5 in Macrophage Inflammation During Osteoarthritis

Inflammation ◽  
2019 ◽  
Vol 42 (5) ◽  
pp. 1821-1829 ◽  
Author(s):  
Zhiming Ni ◽  
Xinhua Zhao ◽  
Xingqin Dai ◽  
Lu Zhao ◽  
Junjie Xia
Keyword(s):  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5

scholarly journals Relating Interferon Regulatory Factor 5 Rs2004640 Gene Polymorphism To Increased Risk Of Systemic Sclerosis In The Patients: Russian Federation Cohort

2020 ◽  
Vol 9 (4) ◽  
Author(s):  
Mikhail Yu. Krylov ◽  
Lidia P. Ananieva ◽  
Irina A. Guseva
Keyword(s):  
Systemic Sclerosis ◽  
Connective Tissue ◽  
Gene Polymorphism ◽  
Connective Tissue Diseases ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Type 1 Interferon ◽  
Interferon Regulatory Factor 5

Background ― A number of studies confirmed a crucial role of type 1 interferon in pathophysiology of connective tissue diseases. Interferon regulatory factors (IRF) coordinate an expression of type 1 interferon, while interferon regulatory factor 5 (IRF5) gene was recently identified as causing predisposition to systemic lupus erythematosus and Sjögren syndrome. The objective of our study was to identify possible association of IRF5 rs2004640 (G/T) single nucleotide polymorphism with systemic sclerosis (SSc). Material and Methods―The study involved 236 individuals, including 105 patients with SSc diagnosis and 131 control individuals from Moscow region. The latter were healthy, unrelated to each other, their genders and ages were matched to those of SSc patients. Allele-specific real-time polymerase chain reaction (PCR) was used to study IFR5 rs2004640 polymorphism. Results ― We detected significantly higher percentage of IRF5 T-allele carriers in all patients (59.5%), those with diffuse cutaneous SSc (67.3%), patients with interstitial lung lesions (62.3%), and those with positive titers of anti-topoisomerase I antibodies (66.3%), compared with control group (46.2%). The odds ratios (OR) were: 1.71 (р=0.00), 2.40 (р=0.0004), 1.93 (р=0.002), and 2.30 (р=0.0008), correspondingly. Conclusion ― The replacement of nucleotide G by T in the IRF5 rs2004640 gene polymorphism was associated with a predisposition to SSc. Our data implied an existence of a novel SSc pathogenetic pathway associated with important role of type 1 interferon in pathophysiology of connective tissue diseases.

Association of Polymorphisms in Interferon Regulatory Factor 5 Gene with Rheumatoid Arthritis: A Metaanalysis

2009 ◽  
Vol 36 (4) ◽  
pp. 693-697 ◽  
Author(s):  
SEUNG WOO HAN ◽  
WON KI LEE ◽  
KI TAE KWON ◽  
BYUNG KI LEE ◽  
EON JEONG NAM ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interferon Regulatory Factor ◽  
Nucleotide Polymorphisms ◽  
Regulatory Factor ◽  
Case Control Studies ◽  
Single Nucleotide ◽  
Funnel Plot ◽  
Interferon Regulatory Factor 5 ◽  
Regression Test

Objective.We investigated potential associations between rheumatoid arthritis (RA) and interferon regulatory factor 5 (IRF5) polymorphisms in a metaanalysis.Methods.This metaanalysis included 5 case-control studies, which provided a total of 6582 RA cases and 5375 controls. Odds ratios (OR) were employed to evaluate the risk of RA according to the 4 single-nucleotide polymorphisms (SNP) inIRF5(rs729302, rs2004640, rs752637, and rs2280714) and data were analyzed in respect to association between alleles.Results.Among 4 candidate SNP, rs729302, rs2004640, and rs2280714 were statistically significant; both allele C of rs729302 and allele G of rs2004640 within the promoter region ofIRF5were associated with a protective effect [random-effects (RE) OR 0.889, 95% confidence interval (CI) 0.803–0.977, p = 0.015 for rs729302; and RE OR 0.905, 95% CI 0.848–0.965, p = 0.002 for rs2004640]. Similar results were also obtained in T allele of rs2280714 in the 3’-untranslated region (RE OR 0.927, 95% CI 0.866–0.992, p = 0.029). There was no evidence of publication bias from funnel-plot asymmetry and Egger’s regression test.Conclusion.Our metaanalysis supported the evidence of the significant role ofIRF5polymorphisms in RA.

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