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Interferon lambda in inflammation and autoimmune rheumatic diseases.

ABSTRACT: Interferons are potent antiviral cytokines that modulate immunity in response to infection or other danger signals. In addition to their antiviral functions, type I interferons (IFNα and IFNβ) are important in the pathogenesis of autoimmune diseases. Type III interferons (IFNλs) were initially described as a specialized system that inhibits viral replication at epithelial barrier surfaces while limiting inflammatory damage. However, evidence now suggests that type III interferons have complex effects on both innate and adaptive immune responses and might also be pathogenic in systemic autoimmune diseases. Concentrations of IFNλs are increased in blood and tissues in a number of autoimmune rheumatic diseases, including systemic lupus erythematosus, and are further associated with specific clinical and laboratory parameters. This Review is aimed at providing a critical evaluation of the current literature on IFNλ biology and how type III interferons might contribute to immune dysregulation and tissue damage in autoimmunity. The potential effects of type III interferons on treatment strategies for autoimmune rheumatic diseases, such as interferon blockade, are also considered.

SUBMITTER: Goel RR

PROVIDER: S-EPMC8077192 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Interferon lambda in inflammation and autoimmune rheumatic diseases.

Goel Rishi R RR Kotenko Sergei V SV Kaplan Mariana J MJ

Nature reviews. Rheumatology 20210427 6

Interferons are potent antiviral cytokines that modulate immunity in response to infection or other danger signals. In addition to their antiviral functions, type I interferons (IFNα and IFNβ) are important in the pathogenesis of autoimmune diseases. Type III interferons (IFNλs) were initially described as a specialized system that inhibits viral replication at epithelial barrier surfaces while limiting inflammatory damage. However, evidence now suggests that type III interferons have complex ef ...[more]

PMID: 33907323

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Project description:Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis. Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage and dendritic cell polarization, and subsequent priming, activation, and proliferation of pathogen-specific T- and B-cells may also be important elements associated with infectious disease outcomes. This review summarizes the emerging details of the IFN-λ immunobiology in the context of the host immune response and viral and bacterial infections.

Dataset Information

Interferon lambda in inflammation and autoimmune rheumatic diseases.

Publications

Interferon lambda in inflammation and autoimmune rheumatic diseases.

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