IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex

Sergei V. Kotenko, Grant Gallagher, Vitality V. Baurin, Anita Lewis-Antes, Meiling Shen, Nital K. Shah, Jerome A. Langer, Faruk Sheikh, Harold Dickensheets, Raymond P. Donnelly

Research output: Contribution to journalReview articlepeer-review

1630 Scopus citations

Abstract

We report here the identification of a ligand-receptor system that, upon engagement, leads to the establishment of an antiviral state. Three closely positioned genes on human chromosome 19 encode distinct but paralogous proteins, which we designate interferon-λI (IFN-λI), IFN-λ2 and IFN-λ3 (tentatively designated as IL-29, IL-28A and IL-28B, respectively, by HUGO).The expression of IFN-λ mRNAs was inducible by viral infection in several cell lines. We identified a distinct receptor complex that is utilized by all three IFN-λ proteins for signaling and is composed of two subunits, a receptor designated CRF2-12 (also designated as IFN-λRI) and a second subunit, CRF2-4 (also known as IL-10R2). Both receptor chains are constitutively expressed on a wide variety of human cell lines and tissues and signal through the Jak-STAT (Janus kinases-signal transducers and activators of transcription) pathway. This receptor-ligand system may contribute to antiviral or other defenses by a mechanism similar to, but independent of, type 1 IFNs.

Original languageEnglish (US)
Pages (from-to)69-77
Number of pages9
JournalNature Immunology
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2003

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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