IL-27 suppresses type 2 immune responses in vivo via direct effects on group 2 innate lymphoid cells

Mucosal Immunol. 2016 Nov;9(6):1384-1394. doi: 10.1038/mi.2016.20. Epub 2016 Mar 16.

Abstract

Group 2 innate lymphoid cells (ILC2) were recently characterized by their ability to produce significant amounts of type-2 signature cytokines and drive central beneficial and pathological features of type-2 immune responses. Although factors such as IL-33 and IL-25 were shown to have ILC2 activating capacity, it is not well understood, how ILC2 responses are regulated in vivo. Here we provide compelling evidence that IL-27-signalling directly inhibits ILC2 responses and reveal a novel mechanism for negative regulation of the innate arm of type-2 immunity. We demonstrate that IL-27-deficiency is linked to increased mucosal presence of ILC2 in a model of inflammatory lung disease. Moreover, IL-27-treatment inhibited ILC2 proliferation and cytokine production and significantly reduced their accumulation in vivo. During helminth infection, regulation of ILC2 by IL-27 directly impacted anti-parasitic immunity. Thus, therapeutic modulation of the IL-27/IL-27R axis may be relevant in a number of inflammatory conditions associated with dysregulated type-2 responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Host-Parasite Interactions / immunology
  • Immunity, Innate*
  • Immunomodulation*
  • Interleukin-27 / genetics
  • Interleukin-27 / metabolism*
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Parasites / immunology
  • Receptors, Interleukin / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • Interleukin-27
  • Receptors, Interleukin
  • STAT3 Transcription Factor