1,077 results match your criteria ifn-induced gene

Effects of Peptide-Induced Immune Tolerance on Murine Lupus.

Front Immunol 2021 19;12:662901. Epub 2021 May 19.

Research Service, Veteran Administration Greater Los Angeles Healthcare System, Los Angeles, CA, United States.

The regulation of autoimmunity and the molecular mechanisms by which different immune cells, including T cells, polymorphonuclear leukocytes (PMN-granulocytes), and B cells suppress autoimmune diseases is complex. We have shown previously that BWF1 lupus mice are protected from autoimmunity after injection or oral administration of tolerogenic doses of pCons, an artificial synthetic peptide based on sequences containing MHC class I and MHC class II determinants in the VH region of a J558-encoded BWF1 anti-DNA Ab. Several T cell subsets can transfer this tolerance. Read More

View Article and Full-Text PDF

Oncolytic Vaccinia Virus Expressing White-Spotted Charr Lectin Regulates Antiviral Response in Tumor Cells and Inhibits Tumor Growth In Vitro and In Vivo.

Mar Drugs 2021 May 21;19(6). Epub 2021 May 21.

College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.

Oncolytic vaccina virus (oncoVV) used for cancer therapy has progressed in recent years. Here, a gene encoding white-spotted charr lectin (WCL) was inserted into an oncoVV vector to form an oncoVV-WCL recombinant virus. OncoVV-WCL induced higher levels of apoptosis and cytotoxicity, and replicated faster than control virus in cancer cells. Read More

View Article and Full-Text PDF

STAT1 N-terminal domain discriminatively controls type I and type II IFN signaling.

Cytokine 2021 Aug 14;144:155552. Epub 2021 May 14.

Department of Toxicology, University Medical Center, Obere Zahlbacher Str. 67, 55131 Mainz, Germany. Electronic address:

The seven signal transducers of transcription (STATs) are cytokine-inducible modular transcription factors. They transmit the stimulation of cells with type I interferons (IFN-α/IFN-β) and type II interferon (IFN-ɣ) into altered gene expression patterns. The N-terminal domain (NTD) of STAT1 is a surface for STAT1/STAT1 homodimer and STAT1/STAT2 heterodimer formation and allows the cooperative DNA binding of STAT1. Read More

View Article and Full-Text PDF

Differential inhibition of HIV replication by the 12 interferon-α subtypes.

J Virol 2021 May 12. Epub 2021 May 12.

INSERM UMR-1124, Paris, France

Type-I interferons (IFNs) are a family of cytokines that represent a first line of defense against virus infections. The 12 different IFN-? subtypes share a common receptor on target cells and trigger similar signaling cascades. Several studies have collectively shown that this apparent redundancy conceals qualitatively different responses induced by individual subtypes, which display different efficacies of inhibition of HIV replication. Read More

View Article and Full-Text PDF

Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials.

Lancet Healthy Longev 2021 May 6;2(5):e250-e262. Epub 2021 May 6.

resTORbio, Boston, MA, USA.

Background: The COVID-19 pandemic highlights the need for therapies that improve immune function in older adults, including interferon (IFN)-induced antiviral immunity that declines with age. In a previous phase 2a trial, RTB101 (previously known as BEZ235), an oral mechanistic target of rapamycin (mTOR) inhibitor, was observed to increase IFN-induced antiviral gene expression and decrease the incidence of respiratory tract infections (RTIs) in older adults. Therefore, we aimed to investigate whether oral RTB101 upregulated IFN-induced antiviral responses and decreased the incidence of viral RTIs when given once daily for 16 weeks during winter cold and flu season. Read More

View Article and Full-Text PDF

Crosstalk Between SUMO and Ubiquitin-Like Proteins: Implication for Antiviral Defense.

Front Cell Dev Biol 2021 21;9:671067. Epub 2021 Apr 21.

Institute for Research in Immunology and Cancer, Montréal, QC, Canada.

Interferon (IFN) is a crucial first line of defense against viral infection. This cytokine induces the expression of several IFN-Stimulated Genes (ISGs), some of which act as restriction factors. Upon IFN stimulation, cells also express ISG15 and SUMO, two key ubiquitin-like (Ubl) modifiers that play important roles in the antiviral response. Read More

View Article and Full-Text PDF

Mesenchymal Stem Cells Antagonize IFN-Induced Proinflammatory Changes and Growth Inhibition Effects via Wnt/β-Catenin and JAK/STAT Pathway in Human Outer Root Sheath Cells and Hair Follicles.

Int J Mol Sci 2021 Apr 27;22(9). Epub 2021 Apr 27.

Department of Dermatology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea.

Mesenchymal stem cell therapy (MSCT) has been shown to be a new therapeutic option for treating alopecia areata (AA). Outer root sheath cells (ORSCs) play key roles in maintaining the hair follicle structure and supporting the bulge area. In human ORSCs (hORSCs), the mechanism for this process has not been extensively studied. Read More

View Article and Full-Text PDF

Tgf-β1 transcriptionally promotes 90K expression: possible implications for cancer progression.

Cell Death Discov 2021 Apr 22;7(1):86. Epub 2021 Apr 22.

Department of Medical, Oral and Biotechnological Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy.

The 90K protein, also known as Mac-2 BP or LGALS3BP, can activate the immune response in part by increasing major histocompatibility (MHC) class I levels. In studies on a non-immune cell model, the rat FRTL-5 cell line, we observed that transforming growth factor (TGF)-β1, like γ-interferon (IFN), increased 90K levels, despite its immunosuppressive functions and the ability to decrease MHC class I. To explain this paradoxical result, we investigated the mechanisms involved in the TGF-β1 regulation of 90K expression with the aim to demonstrate that TGF-β1 utilizes different molecular pathways to regulate the two genes. Read More

View Article and Full-Text PDF

Identification of IFN-Induced Transmembrane Protein 1 With Prognostic Value in Pancreatic Cancer Using Network Module-Based Analysis.

Front Oncol 2021 22;11:626883. Epub 2021 Mar 22.

Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Despite improvements reported in diagnosis and treatments in recent decades, pancreatic cancer is still characterized by poor prognosis and low survival rate among solid tumors. Intensive interests have grown in exploring novel predictive biomarkers, aiming to enhance the efficiency in early detection and treatment prognosis. In this study, we identified the differentially expressed genes (DEGs) in pancreatic cancer by analyzing five gene expression profiles and established the functional modules according to the functional interaction (FI) network between the DEGs. Read More

View Article and Full-Text PDF

IFIT5 Negatively Regulates the Type I IFN Pathway by Disrupting TBK1-IKKε-IRF3 Signalosome and Degrading IRF3 and IKKε.

J Immunol 2021 May 15;206(9):2184-2197. Epub 2021 Apr 15.

State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China

IFN-induced protein with tetratricopeptide repeats (IFITs), known as canonical IFN-stimulated genes (ISGs), play critical roles in regulating immune responses against pathogens and maintaining homeostasis. How the IFIT5 regulates innate immune responses is rarely reported and remains enigmatic. In this study, we discover that human IFIT5 (hIFIT5) functions as a negative regulator of the type I IFN (IFN) pathway in HEK293T cell lines. Read More

View Article and Full-Text PDF

SARS-CoV-2 Nucleocapsid Protein Targets RIG-I-Like Receptor Pathways to Inhibit the Induction of Interferon Response.

Cells 2021 03 2;10(3). Epub 2021 Mar 2.

BK21 Graduate Program, Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) that has resulted in the current pandemic. The lack of highly efficacious antiviral drugs that can manage this ongoing global emergency gives urgency to establishing a comprehensive understanding of the molecular pathogenesis of SARS-CoV-2. We characterized the role of the nucleocapsid protein (N) of SARS-CoV-2 in modulating antiviral immunity. Read More

View Article and Full-Text PDF

DGCR8 deficiency impairs macrophage growth and unleashes the interferon response to mycobacteria.

Life Sci Alliance 2021 06 26;4(6). Epub 2021 Mar 26.

Institute of Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

The mycobacterial cell wall glycolipid trehalose-6,6-dimycolate (TDM) activates macrophages through the C-type lectin receptor MINCLE. Regulation of innate immune cells relies on miRNAs, which may be exploited by mycobacteria to survive and replicate in macrophages. Here, we have used macrophages deficient in the microprocessor component DGCR8 to investigate the impact of miRNA on the response to TDM. Read More

View Article and Full-Text PDF

Interferons at the crossroad of cell death pathways during gastrointestinal inflammation and infection.

Int J Med Microbiol 2021 Apr 25;311(3):151491. Epub 2021 Feb 25.

Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität (FAU), Erlangen, Germany. Electronic address:

Interferons (IFNs) are pleiotropic immune-modulatory cytokines that are well known for their essential role in host defense against viruses, bacteria, and other pathogenic microorganisms. They can exert both, protective or destructive functions depending on the microorganism, the targeted tissue and the cellular context. Interferon signaling results in the induction of IFN-stimulated genes (ISGs) influencing different cellular pathways including direct anti-viral/anti-bacterial response, immune-modulation or cell death. Read More

View Article and Full-Text PDF

The tyrosine kinase c-Abl potentiates interferon-mediated antiviral immunity by STAT1 phosphorylation.

iScience 2021 Feb 21;24(2):102078. Epub 2021 Jan 21.

Beijing Institute of Biotechnology, Beijing 100850, China.

Interferon (IFN)-induced activation of the signal transducer and activator of transcription (STAT) family is an important event in antiviral immunity. Here, we show that the nonreceptor kinases c-Abl and Arg directly interact with STAT1 and potentiate the phosphorylation of STAT1 on Y701. c-Abl/Arg could mediate STAT1 phosphorylation independent of Janus kinases in the absence of IFNγ and potentiate IFNγ-mediated STAT1 phosphorylation. Read More

View Article and Full-Text PDF
February 2021

Targeting human plasmacytoid dendritic cells through BDCA2 prevents skin inflammation and fibrosis in a novel xenotransplant mouse model of scleroderma.

Ann Rheum Dis 2021 Feb 4. Epub 2021 Feb 4.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK

Objectives: Plasmacytoid dendritic cells (pDC) have been implicated in the pathogenesis of autoimmune diseases, such as scleroderma (SSc). However, this has been derived from indirect evidence using human samples or mouse pDC . We have developed human-specific pDC models to directly identify their role in inflammation and fibrosis, as well as attenuation of pDC function with BDCA2-targeting to determine its therapeutic application. Read More

View Article and Full-Text PDF
February 2021

The baseline interferon signature predicts disease severity over the subsequent 5 years in systemic lupus erythematosus.

Arthritis Res Ther 2021 01 16;23(1):29. Epub 2021 Jan 16.

Division of Rheumatology, Schroeder Arthritis Institute, University Health Network, Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada.

Objectives: Type I interferons (IFNs) play an important role in the pathophysiology of systemic lupus erythematosus (SLE). While cross-sectional data suggest an association between IFN-induced gene expression and SLE disease activity, interest in this as a biomarker of flare has been tempered by a lack of fluctuation with disease activity in the majority of patients. This led us to question whether IFN-induced gene expression might instead be a biomarker of overall disease severity, with patients with high levels spending more time in an active disease state. Read More

View Article and Full-Text PDF
January 2021

The peptide symporter SLC15a4 is essential for the development of systemic lupus erythematosus in murine models.

PLoS One 2021 14;16(1):e0244439. Epub 2021 Jan 14.

DiCE Molecules, South San Francisco, CA, United States of America.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease representing a serious unmet medical need. The disease is associated with the loss of self-tolerance and exaggerated B cell activation, resulting in autoantibody production and the formation of immune complexes that accumulate in the kidney, causing glomerulonephritis. TLR7, an important mediator of the innate immune response, drives the expression of type-1 interferon (IFN), which leads to expression of type-1 IFN induced genes and aggravates lupus pathology. Read More

View Article and Full-Text PDF

TRK-Fused Gene (TFG), a protein involved in protein secretion pathways, is an essential component of the antiviral innate immune response.

PLoS Pathog 2021 01 7;17(1):e1009111. Epub 2021 Jan 7.

Faculty of Pharmacy, Université de Montréal, Montréal, Canada.

Antiviral innate immune response to RNA virus infection is supported by Pattern-Recognition Receptors (PRR) including RIG-I-Like Receptors (RLR), which lead to type I interferons (IFNs) and IFN-stimulated genes (ISG) production. Upon sensing of viral RNA, the E3 ubiquitin ligase TNF Receptor-Associated Factor-3 (TRAF3) is recruited along with its substrate TANK-Binding Kinase (TBK1), to MAVS-containing subcellular compartments, including mitochondria, peroxisomes, and the mitochondria-associated endoplasmic reticulum membrane (MAM). However, the regulation of such events remains largely unresolved. Read More

View Article and Full-Text PDF
January 2021

Expression of IFN-induced Transmembrane Protein 1 in Glomerular Endothelial Cells.

Pediatr Int 2020 Dec 17. Epub 2020 Dec 17.

Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori.

Background: Glomerular endothelial cells (GECs) are directly exposed to circulating viral particles in the glomerulus. Although viral infections may trigger the development of acute kidney injury (AKI) or the worsening of pre-existing chronic kidney disease (CKD), the specific molecular mechanisms underlying antiviral reactions via the activation of endothelial Toll-like receptor 3 (TLR3) signaling in the kidney remain to be determined. Interferon (IFN)-induced transmembrane protein 1 (IFITM1), a member of interferon-stimulated gene (ISG) protein family, is involved in the prevention of viral entry into cerebral vascular endothelial cells, respiratory epithelial cells, and endometrium. Read More

View Article and Full-Text PDF
December 2020

Interactions of the Nipah Virus P, V, and W Proteins across the STAT Family of Transcription Factors.

mSphere 2020 12 16;5(6). Epub 2020 Dec 16.

Center for Microbial Pathogenesis, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA

The Nipah virus (NiV) phosphoprotein (P) gene encodes four proteins. Three of these-P, V, and W-possess a common N-terminal domain but distinct C termini. These proteins interact with immune modulators. Read More

View Article and Full-Text PDF
December 2020

IFIT Proteins Are Involved in CXCL10 Expression in Human Glomerular Endothelial Cells Treated with a Toll-Like Receptor 3 Agonist.

Kidney Blood Press Res 2021 16;46(1):74-83. Epub 2020 Dec 16.

Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

Introduction: Various viruses including a novel coronavirus (SARS-CoV-2) can infect the kidney. When viruses invade the glomeruli from the bloodstream, glomerular endothelial cells (GECs) initiate the innate immune reactions. We investigated the expression of interferon (IFN)-induced protein with tetratricopeptide repeats (IFIT) 1/2/3, antiviral molecules, in human GECs treated with a toll-like receptor (TLR) 3 agonist. Read More

View Article and Full-Text PDF

From Diagnosis to Prognosis: Revisiting the Meaning of Muscle ISG15 Overexpression in Juvenile Inflammatory Myopathies.

Arthritis Rheumatol 2021 Jun 26;73(6):1044-1052. Epub 2021 Apr 26.

Institut Mondor de Recherche Biomédicale, Université Paris-Est Créteil, INSERM, Centre de Reference pour les Maladies Neuromusculaires, Hôpital Necker-Enfants Malades, AP-HP, FILNEMUS, Paris, France.

Objective: Juvenile idiopathic inflammatory/immune myopathies (IIMs) constitute a highly heterogeneous group of disorders with diagnostic difficulties and prognostic uncertainties. Circulating myositis-specific autoantibodies (MSAs) have been recognized as reliable tools for patient substratification. Considering the key role of type I interferon (IFN) up-regulation in juvenile IIM, we undertook the present study to investigate whether IFN-induced 15-kd protein (ISG-15) could be a reliable biomarker for stratification and diagnosis and to better elucidate its role in juvenile IIM pathophysiology. Read More

View Article and Full-Text PDF

Monocyte and bone marrow macrophage transcriptional phenotypes in systemic juvenile idiopathic arthritis reveal TRIM8 as a mediator of IFN-γ hyper-responsiveness and risk for macrophage activation syndrome.

Ann Rheum Dis 2020 Dec 4. Epub 2020 Dec 4.

Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Objectives: Systemic juvenile idiopathic arthritis (SJIA) confers high risk for macrophage activation syndrome (MAS), a life-threatening cytokine storm driven by interferon (IFN)-γ. SJIA monocytes display IFN-γ hyper-responsiveness, but the molecular basis of this remains unclear. The objective of this study is to identify circulating monocyte and bone marrow macrophage (BMM) polarisation phenotypes in SJIA including molecular features contributing to IFN response. Read More

View Article and Full-Text PDF
December 2020

Label-free quantitative proteomic analysis of insect larval and metamorphic molts.

BMC Dev Biol 2020 11 24;20(1):24. Epub 2020 Nov 24.

Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, 266237, China.

Background: Molting is an essential biological process occurring characteristic times throughout the life cycle of holometabolous insects. However, it is not clear how insects determine the direction of molting to remain status quo or to initiate metamorphosis. To explore the functional factors that determine the direction of molts, liquid chromatography-mass spectrometry was used to identify the molecules involved in larval and metamorphic molting, and the differentially expressed proteins (DEPs) were compared in the two processes. Read More

View Article and Full-Text PDF
November 2020

Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis.

Nat Commun 2020 11 4;11(1):5566. Epub 2020 Nov 4.

Laboratory of Immunoregulation and Infection, The Francis Crick Institute, London, NW1 1AT, UK.

Tuberculosis (TB) is a leading cause of mortality due to infectious disease, but the factors determining disease progression are unclear. Transcriptional signatures associated with type I IFN signalling and neutrophilic inflammation were shown to correlate with disease severity in mouse models of TB. Here we show that similar transcriptional signatures correlate with increased bacterial loads and exacerbate pathology during Mycobacterium tuberculosis infection upon GM-CSF blockade. Read More

View Article and Full-Text PDF
November 2020

IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease.

Front Immunol 2020 8;11:581445. Epub 2020 Oct 8.

Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), UNLP, CONICET, CIC PBA, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.

Initially described as Th2 promoter cytokine, more recently, IL-33 has been recognized as an alarmin, mainly in epithelial and endothelial cells. While localized in the nucleus acting as a gene regulator, it can be also released after injury, stress or inflammatory cell death. As proinflammatory signal, IL-33 binds to the surface receptor ST2, which enhances mast cell, Th2, regulatory T cell, and innate lymphoid cell type 2 functions. Read More

View Article and Full-Text PDF
October 2020

USP39 Serves as a Deubiquitinase to Stabilize STAT1 and Sustains Type I IFN-Induced Antiviral Immunity.

J Immunol 2020 12 30;205(11):3167-3178. Epub 2020 Oct 30.

Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China

Deubiquitinating enzymes (DUBs) are cysteine proteases that reverse the ubiquitination by removing ubiquitins from the target protein. The human genome encodes ∼100 potential DUBs, which can be classified into six families, influencing multiple cellular processes, such as antiviral responses, inflammatory responses, apoptosis, etc. To systematically explore the role of DUBs involved in antiviral immunity, we performed an RNA interference-based screening that contains 97 human DUBs. Read More

View Article and Full-Text PDF
December 2020

Enhancement of HIV-1 Env-Specific CD8 T Cell Responses Using Interferon-Stimulated Gene 15 as an Immune Adjuvant.

J Virol 2020 12 22;95(2). Epub 2020 Dec 22.

Department of Preventive Medicine and Public Health and Microbiology, Universidad Autónoma de Madrid, Madrid, Spain

Induction of the endogenous innate immune system by interferon (IFN) triggers the expression of many proteins that serve like alarm bells in the body, activating an immune response. After a viral infection, one of the genes activated by IFN induction is the IFN-stimulated gene 15 (), which encodes a ubiquitin-like protein that undergoes a reversible posttranslational modification (ISGylation). ISG15 protein can also act unconjugated, intracellularly and secreted, acting as a cytokine. Read More

View Article and Full-Text PDF
December 2020

Feline calicivirus strain 2280 p30 antagonizes type I interferon-mediated antiviral innate immunity through directly degrading IFNAR1 mRNA.

PLoS Pathog 2020 10 19;16(10):e1008944. Epub 2020 Oct 19.

Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, P. R. China.

Feline calicivirus (FCV) belongs to the Caliciviridae, which comprises small RNA viruses of both medical and veterinary importance. Once infection has occurred, FCV can persist in the cat population, but the molecular mechanism of how it escapes the innate immune response is still unknown. In this study, we found FCV strain 2280 to be relatively resistant to treatment with IFN-β. Read More

View Article and Full-Text PDF
October 2020

A simple and highly efficient method of IFI44L methylation detection for the diagnosis of systemic lupus erythematosus.

Clin Immunol 2020 12 16;221:108612. Epub 2020 Oct 16.

Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China; Research Unit of Key Technologies of Diagnosis and Treatment for Immune-related Skin Diseases, Chinese Academy of Medical Sciences (2019RU027), Changsha, Hunan, China. Electronic address:

Systemic lupus erythematosus (SLE) is a complex heterogenous autoimmune disease that can be challenging to diagnose. We previously identified the IFN-induced protein 44-like (IFI44L) methylation marker for SLE diagnosis, which can be detected by pyrosequencing. Although the previous technique has high sensitivity and specificity, it requires special equipment and high cost for detection. Read More

View Article and Full-Text PDF
December 2020