Constitutive type I interferon modulates homeostatic balance through tonic signaling

Immunity. 2012 Feb 24;36(2):166-74. doi: 10.1016/j.immuni.2012.01.011.


Interferons (IFNs) were discovered as cytokines induced during and protecting from viral infection. They have been documented to play essential roles in numerous physiological processes beyond antiviral and antimicrobial defense, including immunomodulation, cell cycle regulation, cell survival, and cell differentiation. Recent data have also uncovered a potentially darker side to IFN, including roles in inflammatory diseases, such as autoimmunity and diabetes. IFN can have effects in the absence of acute infection, highlighting a physiologic role for constitutive IFN. Type I IFNs are constitutively produced at vanishingly low quantities and yet exert profound effects, mediated in part through modulation of signaling intermediates required for responses to diverse cytokines. We review evidence for a yin-yang of IFN function through its role in modulating crosstalk between multiple cytokines by both feedforward and feedback regulation of common signaling intermediates and postulate a homeostatic role for IFN through tonic signaling in the absence of acute infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / metabolism
  • Antiviral Agents / immunology
  • Antiviral Agents / metabolism
  • Autoimmunity
  • Cytokines / physiology
  • Feedback, Physiological
  • Homeostasis
  • Humans
  • Interferon Type I / genetics
  • Interferon Type I / immunology
  • Interferon Type I / physiology*
  • Promoter Regions, Genetic
  • Signal Transduction
  • Transcription Factors / metabolism


  • Antineoplastic Agents
  • Antiviral Agents
  • Cytokines
  • Interferon Type I
  • Transcription Factors