IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs

Nat Immunol. 2016 Jun;17(6):636-45. doi: 10.1038/ni.3444. Epub 2016 Apr 25.

Abstract

Group 2 innate lymphoid cells (ILC2s) secrete type 2 cytokines, which protect against parasites but can also contribute to a variety of inflammatory airway diseases. We report here that interleukin 1β (IL-1β) directly activated human ILC2s and that IL-12 induced the conversion of these activated ILC2s into interferon-γ (IFN-γ)-producing ILC1s, which was reversed by IL-4. The plasticity of ILCs was manifested in diseased tissues of patients with severe chronic obstructive pulmonary disease (COPD) or chronic rhinosinusitis with nasal polyps (CRSwNP), which displayed IL-12 or IL-4 signatures and the accumulation of ILC1s or ILC2s, respectively. Eosinophils were a major cellular source of IL-4, which revealed cross-talk between IL-5-producing ILC2s and IL-4-producing eosinophils. We propose that IL-12 and IL-4 govern ILC2 functional identity and that their imbalance results in the perpetuation of type 1 or type 2 inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Plasticity*
  • Cells, Cultured
  • Eosinophils / immunology*
  • Female
  • Humans
  • Immunity, Innate*
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism*
  • Interleukin-1beta / metabolism*
  • Interleukin-4 / metabolism*
  • Lymphocyte Activation
  • Lymphocytes / immunology*
  • Mice
  • Mice, SCID
  • Nasal Polyps / immunology*
  • Pneumonia / immunology*
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Rhinitis / immunology*
  • Sinusitis / immunology*
  • Th1 Cells / immunology
  • Th1-Th2 Balance
  • Th2 Cells / immunology

Substances

  • Interleukin-1beta
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma