Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells

Nat Immunol. 2016 Jan;17(1):65-75. doi: 10.1038/ni.3308. Epub 2015 Nov 23.

Abstract

Viral respiratory tract infections are the main causative agents of the onset of infection-induced asthma and asthma exacerbations that remain mechanistically unexplained. Here we found that deficiency in signaling via type I interferon receptor led to deregulated activation of group 2 innate lymphoid cells (ILC2 cells) and infection-associated type 2 immunopathology. Type I interferons directly and negatively regulated mouse and human ILC2 cells in a manner dependent on the transcriptional activator ISGF3 that led to altered cytokine production, cell proliferation and increased cell death. In addition, interferon-γ (IFN-γ) and interleukin 27 (IL-27) altered ILC2 function dependent on the transcription factor STAT1. These results demonstrate that type I and type II interferons, together with IL-27, regulate ILC2 cells to restrict type 2 immunopathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Immunity, Innate / immunology*
  • Interferon Type I / immunology*
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae Infections / immunology
  • Real-Time Polymerase Chain Reaction
  • Respiratory Tract Infections / immunology*
  • Respiratory Tract Infections / pathology

Substances

  • Cytokines
  • Interferon Type I