Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways

Candice Mazewski, Ricardo E. Perez, Eleanor N. Fish, Leonidas C. Platanias*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

88 Scopus citations


For several decades there has been accumulating evidence implicating type I interferons (IFNs) as key elements of the immune response. Therapeutic approaches incorporating different recombinant type I IFN proteins have been successfully employed to treat a diverse group of diseases with significant and positive outcomes. The biological activities of type I IFNs are consequences of signaling events occurring in the cytoplasm and nucleus of cells. Biochemical events involving JAK/STAT proteins that control transcriptional activation of IFN-stimulated genes (ISGs) were the first to be identified and are referred to as “canonical” signaling. Subsequent identification of JAK/STAT-independent signaling pathways, critical for ISG transcription and/or mRNA translation, are denoted as “non-canonical” or “non-classical” pathways. In this review, we summarize these signaling cascades and discuss recent developments in the field, specifically as they relate to the biological and clinical implications of engagement of both canonical and non-canonical pathways.

Original languageEnglish (US)
Article number606456
JournalFrontiers in immunology
StatePublished - Nov 23 2020


  • COVID-19
  • MAP kinase signaling
  • SARS-CoV-2
  • interferon
  • mRNA translation
  • mammalian target of rapamycin
  • signal transducer and activator of transcription
  • signaling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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