Interferon Lambda: Modulating Immunity in Infectious Diseases
Identifieur interne : 000E95 ( Main/Exploration ); précédent : 000E94; suivant : 000E96Interferon Lambda: Modulating Immunity in Infectious Diseases
Auteurs : Mohammedyaseen Syedbasha [Suisse] ; Adrian Egli [Suisse]Source :
- Frontiers in Immunology [ 1664-3224 ] ; 2017.
Abstract
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
Url:
DOI: 10.3389/fimmu.2017.00119
PubMed: 28293236
PubMed Central: 5328987
Affiliations:
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<author><name sortKey="Egli, Adrian" sort="Egli, Adrian" uniqKey="Egli A" first="Adrian" last="Egli">Adrian Egli</name>
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<series><title level="j">Frontiers in Immunology</title>
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<front><div type="abstract" xml:lang="en"><p>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 <italic>via</italic>
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 <italic>Staphylococcus aureus</italic>
and <italic>Mycobacterium tuberculosis</italic>
. 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 <italic>via</italic>
the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions <italic>via</italic>
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.</p>
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