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Updated: Jul 27, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

Cross talk of the interferon-alpha/beta signalling complex with gp130 for effective interleukin-6 signalling

Y Mitani1, A Takaoka, S H Kim

  • 1Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|July 28, 2001
PubMed

Insights

A weak interferon-alpha/beta (IFN-α/β) signal primes cells for robust responses to interleukin-6 (IL-6) and interferon-gamma (IFN-γ). This priming involves IFN-α/β receptor (IFNAR-1) acting as docking sites for transcription factors, enhancing cytokine signaling.

Area of Science:

  • Cellular signaling
  • Immunology
  • Molecular biology

Background:

  • Signaling cross-talk is crucial for cellular responses to cytokines.
  • Previously, the role of the interferon-alpha/beta (IFN-α/β) signaling complex in IFN-γ signaling was established.

Purpose of the Study:

  • To investigate the role of the IFN-α/β signaling complex in interleukin-6 (IL-6) signaling.
  • To elucidate the molecular mechanisms underlying this cross-talk.

Main Methods:

  • In vitro and in vivo experiments assessing IL-6-induced transcription factor activation and gene induction.
  • Cytoplasmic tyrosine residue analysis of IFNAR-1.
  • Chemical cross-linking experiments to determine receptor proximity.

Main Results:

  • The IFN-α/β signaling complex significantly contributes to IL-6-induced activation of Stat1 and Stat3 transcription factors.
  • Absence of the IFN-α/β complex diminishes IL-6 target gene induction.
  • Phosphorylated tyrosine residues on IFNAR-1 serve as docking sites for Stat1 and Stat3.
  • IFNAR-1 and gp130 (an IL-6 family signal transducer) were found in close proximity.

Conclusions:

  • A constitutive weak IFN-α/β signal enhances cellular responses to IL-6, IFN-γ, and potentially other cytokines.
  • These findings suggest the formation of a 'receptosome'-like structure facilitating cytokine signaling cross-talk.
Abstract

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