scholarly journals The Role of Type 1 Interferon in Systemic Sclerosis

2013 ◽  
Vol 4 ◽  
Author(s):  
Minghua Wu ◽  
Shervin Assassi
Keyword(s):  
Systemic Sclerosis ◽  
Type 1 Interferon

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.

[P3-131]: ROLE OF TYPE 1 INTERFERON SIGNALLING ON PATHOGENIC TAU CLEARANCE

2017 ◽  
Vol 13 (7S_Part_20) ◽  
pp. P985-P985
Author(s):  
Pritam Das ◽  
Anna Carrano ◽  
Christophe Verbeeck
Keyword(s):  
Type 1 Interferon ◽  
Interferon Signalling

scholarly journals RNA-Seq analysis identifies novel roles for the primary cilia gene SPAG17 and the SOX9 locus non-coding RNAs in systemic sclerosis

2021 ◽  
Author(s):  
Elisha D.O. Roberson ◽  
Mary Carns ◽  
Li Cao ◽  
Kathleen Aren ◽  
Isaac A. Goldberg ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Mononuclear Cells ◽  
Case Control ◽  
Rna Seq ◽  
Peripheral Blood Mononuclear ◽  
Local Skin ◽  
Type 1 Interferon ◽  
Skin Score ◽  
Non Coding Rnas

Systemic sclerosis (SSc) is characterized by immune activation, vasculopathy, and unresolving fibrosis in the skin, lungs, and other organs. We performed RNA-Seq analysis on skin biopsies and peripheral blood mononuclear cells (PBMCs) from SSc patients and controls to better understand SSc pathogenesis. We analyzed these data to 1) test for case-control differences, and 2) identify genes whose expression levels correlate with SSc severity as measured by local skin score, modified Rodnan skin score (MRSS), forced vital capacity (FVC), or diffusion capacity for carbon monoxide (DLCO). We found that PBMCs from SSc patients showed a strong type 1 interferon signature. This signal replicated in the skin, with additional signals for increased extracellular matrix (ECM) genes, classical complement pathway activation, and the presence of B cells. Notably, we observed a marked decrease in the expression of SPAG17, a cilia component, in SSc skin. We identified genes that correlated with MRSS, DLCO, and FVC in SSc PBMCs and skin using weighted gene co-expression analysis (WGCNA). These genes were largely distinct from the case/control differentially expressed genes. In PBMCs, type 1 interferon signatures negatively correlated with DLCO. In SSc skin, ECM gene expression positively correlated with MRSS. Network analysis of SSc skin genes correlated with clinical features identified the non-coding RNAs SOX9-AS1 and ROCR, both near the SOX9 locus, as highly connected,"hub-like" genes in the network. These results identify non-coding RNAs and SPAG17 as novel factors potentially implicated in SSc pathogenesis.

scholarly journals High basal STAT4 balanced by STAT1 induction to control type 1 interferon effects in natural killer cells

2007 ◽  
Vol 204 (10) ◽  
pp. 2383-2396 ◽  
Author(s):  
Takuya Miyagi ◽  
M. Pilar Gil ◽  
Xin Wang ◽  
Jennifer Louten ◽  
Wen-Ming Chu ◽  
...  
Keyword(s):  
Nk Cells ◽  
Signaling Pathways ◽  
Nk Cell ◽  
Critical Role ◽  
Unique Role ◽  
Type 1 Interferon ◽  
Ifn Γ

The best-characterized type 1 interferon (IFN) signaling pathway depends on signal transducer and activator of transcription 1 (STAT1) and STAT2. The cytokines can, however, conditionally activate all STATs. Regulation of their access to particular signaling pathways is poorly understood. STAT4 is important for IFN-γ induction, and NK cells are major producers of this cytokine. We report that NK cells have high basal STAT4 levels and sensitivity to type 1 IFN–mediated STAT4 activation for IFN-γ production. Increases in STAT1, driven during viral infection by either type 1 IFN or IFN-γ, are associated with decreased STAT4 access. Both STAT1 and STAT2 are important for antiviral defense, but STAT1 has a unique role in protecting against sustained NK cell IFN-γ production and resulting disease. The regulation occurs with an NK cell type 1 IFN receptor switch from a STAT4 to a STAT1 association. Thus, a fundamental characteristic of NK cells is high STAT4 bound to the type 1 IFN receptor. The conditions of infection result in STAT1 induction with displacement of STAT4. These studies elucidate the critical role of STAT4 levels in predisposing selection of specific signaling pathways, define the biological importance of regulation within particular cell lineages, and provide mechanistic insights for how this is accomplished in vivo.

scholarly journals Architectural B-cell organization in skeletal muscle identifies subtypes of dermatomyositis

2018 ◽  
Vol 5 (3) ◽  
pp. e451 ◽  
Author(s):  
Josefine Radke ◽  
Randi Koll ◽  
Corinna Preuße ◽  
Debora Pehl ◽  
Kremena Todorova ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
B Cells ◽  
B Cell ◽  
Type I ◽  
Cell Content ◽  
Interferon Signature ◽  
Type 1 Interferon ◽  
Cell Immunity

ObjectiveTo study the B-cell content, organization, and existence of distinct B-cell subpopulations in relation to the expression of type 1 interferon signature related genes in dermatomyositis (DM).MethodsEvaluation of skeletal muscle biopsies from patients with adult DM (aDM) and juvenile DM (jDM) by histology, immunohistochemistry, electron microscopy, and quantitative reverse-transcription PCR.ResultsWe defined 3 aDM subgroups—classic (containing occasional B cells without clusters), B-cell–rich, and follicle-like aDM—further elucidating IM B-lymphocyte maturation and immunity. The quantity of B cells and formation of ectopic lymphoid structures in a subset of patients with aDM were associated with a specific profile of cytokines and chemokines involved in lymphoid neogenesis. Levels of type 1 interferon signature related gene expression paralleled B-cell content and architectural organization and link B-cell immunity to the interferon type I signature.ConclusionThese data corroborate the important role of B cells in DM, highlighting the direct link between humoral mechanisms as key players in B-cell immunity and the role of type I interferon–related immunity.

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