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

Nat Immunol. 2003 Jan;4(1):69-77. doi: 10.1038/ni875. Epub 2002 Dec 16.


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-lambda1 (IFN-lambda1), IFN-lambda2 and IFN-lambda3 (tentatively designated as IL-29, IL-28A and IL-28B, respectively, by HUGO). The expression of IFN-lambda mRNAs was inducible by viral infection in several cell lines. We identified a distinct receptor complex that is utilized by all three IFN-lambda proteins for signaling and is composed of two subunits, a receptor designated CRF2-12 (also designated as IFN-lambdaR1) 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 I IFNs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antiviral Agents / metabolism
  • Base Sequence
  • COS Cells
  • Cell Line
  • Chromosomes, Human, Pair 19 / genetics
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Humans
  • Interferons / classification
  • Interferons / genetics
  • Interferons / metabolism*
  • Interleukin-10 Receptor beta Subunit
  • Ligands
  • Macromolecular Substances
  • Membrane Glycoproteins*
  • Molecular Sequence Data
  • Receptors, Cytokine / classification
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Virus Diseases / immunology


  • Antiviral Agents
  • DNA, Complementary
  • IL10RB protein, human
  • Interleukin-10 Receptor beta Subunit
  • Ligands
  • Macromolecular Substances
  • Membrane Glycoproteins
  • Receptors, Cytokine
  • Recombinant Proteins
  • Interferons

Associated data

  • GENBANK/AF439325
  • GENBANK/AX355968
  • GENBANK/AY184373
  • GENBANK/AY184374
  • GENBANK/AY184375
  • GENBANK/AY184376