Shared and Distinct Functions of Type I and Type III Interferons

• 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
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2019.03.025

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.