Shared and Distinct Functions of Type I and Type III Interferons

Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs. However, recent discoveries have revealed context-specific functional differences. Here, we provide...

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Published in	Immunity (Cambridge, Mass.) Vol. 50; no. 4; pp. 907 - 923
Main Authors	Lazear, Helen M., Schoggins, John W., Diamond, Michael S.
Format	Journal Article
Language	English
Published	United States Elsevier Inc 16.04.2019 Elsevier Limited
Subjects	Adaptive Immunity Animals Antiviral Agents - therapeutic use Autoimmune Diseases - etiology Autoimmune Diseases - immunology Binding sites Chromosomes Cytokines Epithelial Cells - immunology Female Gene expression Humans Infections Inflammation Interferon Interferon Lambda Interferon Type I - adverse effects Interferon Type I - immunology Interferon Type I - therapeutic use Interferons - adverse effects Interferons - immunology Interferons - therapeutic use Leukemia Male Maternal-Fetal Exchange - immunology Melanoma Mice Molecular modelling Multiple sclerosis Neoplasms - drug therapy Neoplasms - immunology Neutrophils Organ Specificity Physiological responses Pregnancy Priming Signal Transduction - immunology Therapeutic applications Transcription Transcription, Genetic Transcriptome Vertebrates Viral infections Virus Diseases - drug therapy Virus Diseases - immunology α-Interferon β-Interferon
Online Access	Get full text
ISSN	1074-7613 1097-4180 1097-4180
DOI	10.1016/j.immuni.2019.03.025

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Abstract	Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs. However, recent discoveries have revealed context-specific functional differences. Here, we provide a comprehensive review of type I and type III IFN activities, highlighting shared and distinct features from molecular mechanisms through physiological responses. Beyond discussing canonical antiviral functions, we consider the adaptive immune priming, anti-tumor, and autoimmune functions of IFNs. We discuss a model wherein type III IFNs serve as a front-line defense that controls infection at epithelial barriers while minimizing damaging inflammatory responses, reserving the more potent type I IFN response for when local responses are insufficient. In this context, we discuss current therapeutic applications targeting these cytokine pathways and highlight gaps in understanding of the biology of type I and type III IFNs in health and disease. Lazear, Schoggins, and Diamond review the shared and distinct features of type I and III interferons, from molecular mechanisms through physiological responses. In this context, they discuss the current state of interferon-based therapeutic approaches in the clinic and highlight gaps in understanding of the biology of these cytokines.
AbstractList	Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs. However, recent discoveries have revealed context-specific functional differences. Here, we provide a comprehensive review of type I and type III IFN activities, highlighting shared and distinct features from molecular mechanisms through physiological responses. Beyond discussing canonical antiviral functions, we consider the adaptive immune priming, anti-tumor, and autoimmune functions of IFNs. We discuss a model wherein type III IFNs serve as a front-line defense that controls infection at epithelial barriers while minimizing damaging inflammatory responses, reserving the more potent type I IFN response for when local responses are insufficient. In this context, we discuss current therapeutic applications targeting these cytokine pathways and highlight gaps in understanding of the biology of type I and type III IFNs in health and disease. Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs. However, recent discoveries have revealed context-specific functional differences. Here, we provide a comprehensive review of type I and type III IFN activities, highlighting shared and distinct features from molecular mechanisms through physiological responses. Beyond discussing canonical antiviral functions, we consider the adaptive immune priming, anti-tumor, and autoimmune functions of IFNs. We discuss a model wherein type III IFNs serve as a front-line defense that controls infection at epithelial barriers while minimizing damaging inflammatory responses, reserving the more potent type I IFN response for when local responses are insufficient. In this context, we discuss current therapeutic applications targeting these cytokine pathways and highlight gaps in understanding of the biology of type I and type III IFNs in health and disease.Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs. However, recent discoveries have revealed context-specific functional differences. Here, we provide a comprehensive review of type I and type III IFN activities, highlighting shared and distinct features from molecular mechanisms through physiological responses. Beyond discussing canonical antiviral functions, we consider the adaptive immune priming, anti-tumor, and autoimmune functions of IFNs. We discuss a model wherein type III IFNs serve as a front-line defense that controls infection at epithelial barriers while minimizing damaging inflammatory responses, reserving the more potent type I IFN response for when local responses are insufficient. In this context, we discuss current therapeutic applications targeting these cytokine pathways and highlight gaps in understanding of the biology of type I and type III IFNs in health and disease. Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs. However, recent discoveries have revealed context-specific functional differences. Here, we provide a comprehensive review of type I and type III IFN activities, highlighting shared and distinct features from molecular mechanisms through physiological responses. Beyond discussing canonical antiviral functions, we consider the adaptive immune priming, anti-tumor, and autoimmune functions of IFNs. We discuss a model wherein type III IFNs serve as a front-line defense that controls infection at epithelial barriers while minimizing damaging inflammatory responses, reserving the more potent type I IFN response for when local responses are insufficient. In this context, we discuss current therapeutic applications targeting these cytokine pathways and highlight gaps in understanding of the biology of type I and type III IFNs in health and disease. Lazear, Schoggins, and Diamond review the shared and distinct features of type I and III interferons, from molecular mechanisms through physiological responses. In this context, they discuss the current state of interferon-based therapeutic approaches in the clinic and highlight gaps in understanding of the biology of these cytokines.
Author	Schoggins, John W. Diamond, Michael S. Lazear, Helen M.
AuthorAffiliation	4 Lead Contact 2 Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA 1 Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA 3 Departments of Medicine, Pathology & Immunology, and Molecular Microbiology, and The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA
AuthorAffiliation_xml	– name: 2 Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA – name: 1 Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA – name: 4 Lead Contact – name: 3 Departments of Medicine, Pathology & Immunology, and Molecular Microbiology, and The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA
Author_xml	– sequence: 1 givenname: Helen M. surname: Lazear fullname: Lazear, Helen M. email: helen.lazear@med.unc.edu organization: Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 2 givenname: John W. surname: Schoggins fullname: Schoggins, John W. organization: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA – sequence: 3 givenname: Michael S. surname: Diamond fullname: Diamond, Michael S. email: mdiamond@wustl.edu organization: Departments of Medicine, Pathology & Immunology, and Molecular Microbiology, and The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/30995506$$D View this record in MEDLINE/PubMed
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Snippet	Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared...
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SubjectTerms	Adaptive Immunity Animals Antiviral Agents - therapeutic use Autoimmune Diseases - etiology Autoimmune Diseases - immunology Binding sites Chromosomes Cytokines Epithelial Cells - immunology Female Gene expression Humans Infections Inflammation Interferon Interferon Lambda Interferon Type I - adverse effects Interferon Type I - immunology Interferon Type I - therapeutic use Interferons - adverse effects Interferons - immunology Interferons - therapeutic use Leukemia Male Maternal-Fetal Exchange - immunology Melanoma Mice Molecular modelling Multiple sclerosis Neoplasms - drug therapy Neoplasms - immunology Neutrophils Organ Specificity Physiological responses Pregnancy Priming Signal Transduction - immunology Therapeutic applications Transcription Transcription, Genetic Transcriptome Vertebrates Viral infections Virus Diseases - drug therapy Virus Diseases - immunology α-Interferon β-Interferon
Title	Shared and Distinct Functions of Type I and Type III Interferons
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