Structural basis of a unique interferon-β signaling axis mediated via the receptor IFNAR1. Academic Article uri icon

abstract

  • Type I interferons are important in regulating immune responses to pathogens and tumors. All interferons are considered to signal via the heterodimeric IFNAR1-IFNAR2 complex, yet some subtypes such as interferon-β (IFN-β) can exhibit distinct functional properties, although the molecular basis of this is unclear. Here we demonstrate IFN-β can uniquely and specifically ligate to IFNAR1 in an IFNAR2-independent manner, and we provide the structural basis of the IFNAR1-IFN-β interaction. The IFNAR1-IFN-β complex transduced signals that modulated expression of a distinct set of genes independently of Jak-STAT pathways. Lipopolysaccharide-induced sepsis was ameliorated in Ifnar1(-/-) mice but not Ifnar2(-/-) mice, suggesting that IFNAR1-IFN-β signaling is pathologically relevant. Thus, we provide a molecular basis for understanding specific functions of IFN-β.

authors

  • de Weerd, NA
  • Vivian, JP
  • Nguyen, TK
  • Mangan, NE
  • Gould, JA
  • Braniff, S
  • Zaker-Tabrizi, L
  • Fung, KY
  • Forster, SC
  • Beddoe, T
  • Reid, HH
  • Rossjohn, J
  • Hertzog, PJ

publication date

  • 2013