Interferon and IL-27 antagonize the function of group 2 innate lymphoid cells and type 2 innate immune responses

Nat Immunol. 2016 Jan;17(1):76-86. doi: 10.1038/ni.3309. Epub 2015 Nov 23.


Group 2 innate lymphoid cells (ILC2 cells) are type 2 cytokine-producing cells of the innate immune system with important roles in helminth infection and allergic inflammation. Here we found that tissue-resident ILC2 cells proliferated in situ without migrating during inflammatory responses. Both type I and type II interferons and interleukin 27 (IL-27) suppressed ILC2 function in a manner dependent on the transcription factor STAT1. ILC2-mediated lung inflammation was enhanced in the absence of the interferon-γ (IFN-γ) receptor on ILC2 cells in vivo. IFN-γ effectively suppressed the function of tissue-resident ILC2 cells but not that of inflammatory ILC2 cells, and IL-27 suppressed tissue-resident ILC2 cells but not tissue-resident TH2 cells during lung inflammation induced by Alternaria alternata. Our results demonstrate that suppression mediated by interferon and IL-27 is a negative feedback mechanism for ILC2 function in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Disease Models, Animal
  • Flow Cytometry
  • Helminthiasis, Animal / immunology*
  • Immunity, Innate / immunology*
  • Interferons / immunology*
  • Interleukins / immunology*
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pneumonia / immunology
  • Real-Time Polymerase Chain Reaction


  • Il27 protein, mouse
  • Interleukins
  • Interferons

Associated data

  • GEO/GSE73272