Shared and Distinct Functions of Type I and Type III Interferons

By Helen M. Lazear, John W. Schoggins, Michael S. Diamond. Immunity, 2019

1,016 citations recorded by the source corpus.

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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/7b5af7cbf164f38c17b539239c30f0054d36629b

Citations in the corpus

• Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19 (2020, neutral): “induction of type I and III interferons (IFN-I and IFN-III, respectively) and subsequent upregulation of IFN-stimulated genes (ISGs) (Lazear et al., 2019).”
• Host cell-intrinsic innate immune recognition of SARS-CoV-2 (2021, neutral): “ISGs A major response to IFN signaling is the production of ISGs [21].”