IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity

Nat Immunol. 2016 Jun;17(6):646-55. doi: 10.1038/ni.3447. Epub 2016 Apr 25.

Abstract

Group 2 innate lymphoid cells (ILC2 cells) are important for type 2 immune responses and are activated by the epithelial cytokines interleukin 33 (IL-33), IL-25 and thymic stromal lymphopoietin (TSLP). Here we demonstrated that IL-1β was a critical activator of ILC2 cells, inducing proliferation and cytokine production and regulating the expression of epithelial cytokine receptors. IL-1β also governed ILC2 plasticity by inducing low expression of the transcription factor T-bet and the cytokine receptor chain IL-12Rβ2, which enabled the conversion of these cells into an ILC1 phenotype in response to IL-12. This transition was marked by an atypical chromatin landscape characterized by the simultaneous transcriptional accessibility of the locus encoding interferon-γ (IFN-γ) and the loci encoding IL-5 and IL-13. Finally, IL-1β potentiated ILC2 activation and plasticity in vivo, and IL-12 acted as the switch that determined an ILC2-versus-ILC1 response. Thus, we have identified a previously unknown role for IL-1β in facilitating ILC2 maturation and plasticity.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Plasticity* / immunology
  • Cells, Cultured
  • Cytokines / metabolism
  • Humans
  • Immunity, Innate*
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism*
  • Interleukin-17 / metabolism
  • Interleukin-1beta / metabolism*
  • Interleukin-33 / metabolism
  • Lymphocytes / immunology*
  • Mice
  • Mice, SCID
  • Receptors, Interleukin-12 / genetics
  • Receptors, Interleukin-12 / metabolism
  • Signal Transduction
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Th1 Cells / immunology
  • Th1-Th2 Balance
  • Th2 Cells / immunology

Substances

  • Cytokines
  • IL12RB2 protein, human
  • IL25 protein, human
  • IL33 protein, human
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-33
  • Receptors, Interleukin-12
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interleukin-12
  • Interferon-gamma
  • thymic stromal lymphopoietin