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International Journal of Molecular... Sep 2022Antiviral type I interferons (IFN) produced in the early phase of viral infections effectively inhibit viral replication, prevent virus-mediated tissue damages and... (Review)
Review
Antiviral type I interferons (IFN) produced in the early phase of viral infections effectively inhibit viral replication, prevent virus-mediated tissue damages and promote innate and adaptive immune responses that are all essential to the successful elimination of viruses. As professional type I IFN producing cells, plasmacytoid dendritic cells (pDC) have the ability to rapidly produce waste amounts of type I IFNs. Therefore, their low frequency, dysfunction or decreased capacity to produce type I IFNs might increase the risk of severe viral infections. In accordance with that, declined pDC numbers and delayed or inadequate type I IFN responses could be observed in patients with severe coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as compared to individuals with mild or no symptoms. Thus, besides chronic diseases, all those conditions, which negatively affect the antiviral IFN responses lengthen the list of risk factors for severe COVID-19. In the current review, we would like to briefly discuss the role and dysregulation of pDC/type I IFN axis in COVID-19, and introduce those type I IFN-dependent factors, which account for an increased risk of COVID-19 severity and thus are responsible for the different magnitude of individual immune responses to SARS-CoV-2.
Topics: Antiviral Agents; COVID-19; Humans; Interferon Type I; Interferons; SARS-CoV-2; Virus Replication
PubMed: 36142877
DOI: 10.3390/ijms231810968 -
The Journal of Rheumatology Sep 2023Type I interferon (IFN-I) is thought to play a role in many systemic autoimmune diseases. IFN-I pathway activation is associated with pathogenic features, including the... (Review)
Review
Type I interferon (IFN-I) is thought to play a role in many systemic autoimmune diseases. IFN-I pathway activation is associated with pathogenic features, including the presence of autoantibodies and clinical phenotypes such as more severe disease with increased disease activity and damage. We will review the role and potential drivers of IFN-I dysregulation in 5 prototypic autoimmune diseases: systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, primary Sjögren syndrome, and systemic sclerosis. We will also discuss current therapeutic strategies that directly or indirectly target the IFN-I system.
Topics: Humans; Autoimmunity; Interferon Type I; Autoimmune Diseases; Lupus Erythematosus, Systemic; Interferons; Antibodies; Phenotype
PubMed: 37399470
DOI: 10.3899/jrheum.2022-0827 -
International Journal of Molecular... Sep 2021There are three classes of interferons (type 1, 2, and 3) that can contribute to the development and maintenance of various autoimmune diseases, including systemic lupus... (Review)
Review
There are three classes of interferons (type 1, 2, and 3) that can contribute to the development and maintenance of various autoimmune diseases, including systemic lupus erythematosus (SLE). Each class of interferons promotes the generation of autoreactive B cells and SLE-associated autoantibodies by distinct signaling mechanisms. SLE patients treated with various type 1 interferon-blocking biologics have diverse outcomes, suggesting that additional environmental and genetic factors may dictate how these cytokines contribute to the development of autoreactive B cells and SLE. Understanding how each class of interferons controls B cell responses in SLE is necessary for developing optimized B cell- and interferon-targeted therapeutics. In this review, we will discuss how each class of interferons differentially promotes the loss of peripheral B cell tolerance and leads to the development of autoreactive B cells, autoantibodies, and SLE.
Topics: Animals; Autoantibodies; B-Lymphocytes; Humans; Interferons; Lupus Erythematosus, Systemic; Signal Transduction
PubMed: 34638804
DOI: 10.3390/ijms221910464 -
Journal of Innate Immunity 2015Interferon-lambda (IFN-λ), a recently discovered cytokine, overlaps broadly with type I IFN signaling, producing antiviral, antiproliferative, and proapoptotic... (Review)
Review
Interferon-lambda (IFN-λ), a recently discovered cytokine, overlaps broadly with type I IFN signaling, producing antiviral, antiproliferative, and proapoptotic responses. In comparison to type I IFNs, IFN-λ has a limited spectrum of responsive tissues due to variation in expression of the IFN-λ receptor IFNLR1. Type I IFNs have been investigated for their antitumor effects and used in the clinical setting for a number of different cancers. Given the overlap in signaling and function between IFN-λ and type I IFNs, IFN-λ has also drawn interest for the treatment of cancer. To date, a number of studies using both murine and human models of cancer have investigated the antitumor effects of IFN-λ. These studies have found that IFN-λ is capable of directly targeting cancer cells to reduce their tumorigenicity, induce cell cycle arrest, and cause apoptosis. In addition, IFN-λ has been shown to have indirect effects against cancer cells through immune system responses and immune modulatory effects. This review aims to detail the findings of studies investigating IFN-λ for the treatment of cancer as well as suggest areas of potential interest for future studies.
Topics: Humans; Immunologic Factors; Interferons; Neoplasms; Receptors, Cytokine; Receptors, Interferon
PubMed: 25661266
DOI: 10.1159/000370113 -
Biochimie 2007Since the discovery of interferon 50 years ago a great deal of progress has been made in understanding how interferons work and how and why they are induced. Key factors... (Review)
Review
Since the discovery of interferon 50 years ago a great deal of progress has been made in understanding how interferons work and how and why they are induced. Key factors in interferon induction are the interferon regulatory factors (IRF). In this review of IRF we aim to show you not only the historical side of the IRF but also the integral, anti-viral and hematopoetic roles of these transcription factors, as well as the sometimes surprising and even forgotten roles that these proteins play, not only in interferon signaling but throughout the immune system and the body as a whole. Further research will no doubt expand the repertoire of these multifunctional proteins even more.
Topics: Animals; Antiviral Agents; Hematopoiesis; Humans; Immune System; Interferon Regulatory Factors; Interferons; Models, Biological; Repressor Proteins; Response Elements; Signal Transduction; Transcription Factors; Viral Proteins
PubMed: 17399883
DOI: 10.1016/j.biochi.2007.01.014 -
Molecular Oral Microbiology Dec 2019Oral epithelial cells (OEC) represent the first site of host interaction with viruses that infect the body through the oral route; however, their innate antiviral...
Oral epithelial cells (OEC) represent the first site of host interaction with viruses that infect the body through the oral route; however, their innate antiviral defense mechanisms yet to be defined. Previous studies have determined that OEC express pathogen-, damage-, or danger-associated molecular patterns (PAMPs or DAMPs), but their expression of key antiviral innate immune mediators, including type I interferons (type I IFN) and interferon-stimulated genes (ISGs) has not been studied extensively. We used the oral keratinocyte cell line, OKF6/TERT1, in the presence and absence of the viral mimics poly(I:C) and unmethylated CpG DNA, to define the expression of type I IFN and ISGs. We identified the basal expression of novel type I IFN genes IFNE and IFNK, while IFNB1 was induced by viral mimics, through the nuclear translocation of IRF3. Numerous ISGs were expressed at basal levels in OEC, with an apparent correlation between high expression and antiviral activity at the earlier stages of viral infection. Stimulation of OECs with poly(I:C) led to selective induction of ISGs, including MX1, BST2, PML, RSAD2, ISG15, and ZC3HAV1. Together, our results demonstrate that OECs exhibit a robust innate antiviral immune defense profile, which is primed to address a wide variety of pathogenic viruses that are transmitted orally.
Topics: Antiviral Agents; Epithelial Cells; Gene Expression; Humans; Immunity, Innate; Interferon Type I; Interferons; Keratinocytes; RNA-Binding Proteins; Virus Diseases
PubMed: 31520463
DOI: 10.1111/omi.12270 -
Growth Factors (Chur, Switzerland) Jun 2012Interferon cytokine family members shape the immune response to protect the host from both pathologic infections and tumorigenesis. To mediate their physiologic... (Review)
Review
Interferon cytokine family members shape the immune response to protect the host from both pathologic infections and tumorigenesis. To mediate their physiologic function, interferons evoke a robust and complex signal transduction pathway that leads to the induction of interferon-stimulated genes with both proinflammatory and antiviral functions. Numerous mechanisms exist to tightly regulate the extent and duration of these cellular responses. Among such mechanisms, the post-translational conjugation of ubiquitin polypeptides to protein mediators of interferon signaling has emerged as a crucially important mode of control. In this mini-review, we highlight recent advances in our understanding of these ubiquitin-mediated mechanisms, their exploitation by invading viruses, and their possible utilization for medical intervention.
Topics: Amino Acid Sequence; Animals; Gene Expression Regulation; Humans; Interferons; Molecular Sequence Data; Signal Transduction; Ubiquitin; Ubiquitin-Protein Ligases; Ubiquitination; Viruses
PubMed: 22394219
DOI: 10.3109/08977194.2012.669382 -
Cell Metabolism Jan 2024A major hypothesis for the etiology of type 1 diabetes (T1D) postulates initiation by viral infection, leading to double-stranded RNA (dsRNA)-mediated interferon...
A major hypothesis for the etiology of type 1 diabetes (T1D) postulates initiation by viral infection, leading to double-stranded RNA (dsRNA)-mediated interferon response and inflammation; however, a causal virus has not been identified. Here, we use a mouse model, corroborated with human islet data, to demonstrate that endogenous dsRNA in beta cells can lead to a diabetogenic immune response, thus identifying a virus-independent mechanism for T1D initiation. We found that disruption of the RNA editing enzyme adenosine deaminases acting on RNA (ADAR) in beta cells triggers a massive interferon response, islet inflammation, and beta cell failure and destruction, with features bearing striking similarity to early-stage human T1D. Glycolysis via calcium enhances the interferon response, suggesting an actionable vicious cycle of inflammation and increased beta cell workload.
Topics: Mice; Animals; Humans; Diabetes Mellitus, Type 1; RNA Editing; RNA, Double-Stranded; Interferons; Inflammation
PubMed: 38128529
DOI: 10.1016/j.cmet.2023.11.011 -
Frontiers in Immunology 2023
Topics: Interferons; Viruses
PubMed: 37662952
DOI: 10.3389/fimmu.2023.1269413 -
Dermatologic Clinics Oct 2015Interferons are polypeptides that naturally occur in the human body as a part of the innate immune response. By harnessing these immunomodulatory functions, synthetic... (Review)
Review
Interferons are polypeptides that naturally occur in the human body as a part of the innate immune response. By harnessing these immunomodulatory functions, synthetic interferons have shown efficacy in combating various diseases including cutaneous T-cell lymphoma. This article closely examines the qualities of interferon alfa and interferon gamma and the evidence behind their use in the 2 most common types of cutaneous T-cell lymphomas, namely, mycosis fungoides and Sézary syndrome.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Humans; Interferon-alpha; Interferon-beta; Interferon-gamma; Mycosis Fungoides; PUVA Therapy; Retinoids; Skin Neoplasms
PubMed: 26433845
DOI: 10.1016/j.det.2015.05.008