Interleukin-33 and Interferon-γ Counter-Regulate Group 2 Innate Lymphoid Cell Activation during Immune Perturbation

Immunity. 2015 Jul 21;43(1):161-74. doi: 10.1016/j.immuni.2015.05.019. Epub 2015 Jun 16.

Abstract

Group 2 innate lymphoid cells (ILC2s) and regulatory T (Treg) cells are systemically induced by helminth infection but also sustain metabolic homeostasis in adipose tissue and contribute to tissue repair during injury. Here we show that interleukin-33 (IL-33) mediates activation of ILC2s and Treg cells in resting adipose tissue, but also after helminth infection or treatment with IL-2. Unexpectedly, ILC2-intrinsic IL-33 activation was required for Treg cell accumulation in vivo and was independent of ILC2 type 2 cytokines but partially dependent on direct co-stimulatory interactions via ICOSL-ICOS. IFN-γ inhibited ILC2 activation and Treg cell accumulation by IL-33 in infected tissue, as well as adipose tissue, where repression increased with aging and high-fat diet-induced obesity. IL-33 and ILC2s are central mediators of type 2 immune responses that promote tissue and metabolic homeostasis, and IFN-γ suppresses this pathway, likely to promote inflammatory responses and divert metabolic resources necessary to protect the host.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology
  • Animals
  • Diet, High-Fat
  • Enzyme Activation / immunology
  • Inducible T-Cell Co-Stimulator Protein / biosynthesis
  • Inducible T-Cell Co-Stimulator Protein / immunology
  • Interferon-gamma / immunology*
  • Interferon-gamma / pharmacology
  • Interleukin-2 / pharmacology
  • Interleukin-33
  • Interleukins / immunology*
  • Intra-Abdominal Fat / cytology
  • Intra-Abdominal Fat / immunology
  • Listeria monocytogenes / immunology
  • Listeriosis / immunology
  • Listeriosis / microbiology
  • Lung / cytology
  • Lung / immunology
  • Lung / pathology
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Transgenic
  • Nippostrongylus / immunology
  • Obesity / immunology
  • Receptors, Immunologic / biosynthesis
  • Strongylida Infections / immunology*
  • Strongylida Infections / parasitology
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Il33 protein, mouse
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukin-2
  • Interleukin-33
  • Interleukins
  • Klrg1 protein, mouse
  • Receptors, Immunologic
  • Interferon-gamma