Shared and Distinct Functions of Type I and Type III Interferons

Immunity. 2019 Apr 16;50(4):907-923. 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antiviral Agents / therapeutic use
  • Autoimmune Diseases / etiology
  • Autoimmune Diseases / immunology
  • Epithelial Cells / immunology
  • Female
  • Humans
  • Interferon Type I / adverse effects
  • Interferon Type I / immunology*
  • Interferon Type I / therapeutic use
  • Interferons / adverse effects
  • Interferons / immunology*
  • Interferons / therapeutic use
  • Male
  • Maternal-Fetal Exchange / immunology
  • Mice
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Organ Specificity
  • Pregnancy
  • Signal Transduction / immunology
  • Transcription, Genetic
  • Transcriptome
  • Virus Diseases / drug therapy
  • Virus Diseases / immunology


  • Antiviral Agents
  • Interferon Type I
  • interferon type III
  • Interferons