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The helminth T2 RNase ω1 promotes metabolic homeostasis in an IL-33- and group 2 innate lymphoid cell-dependent mechanism

FASEB J. 2016 Feb;30(2):824-35. doi: 10.1096/fj.15-277822. Epub 2015 Oct 21.

Abstract

Induction of a type 2 cellular response in the white adipose tissue leads to weight loss and improves glucose homeostasis in obese animals. Injection of obese mice with recombinant helminth-derived Schistosoma mansoni egg-derived ω1 (ω1), a potent inducer of type 2 activation, improves metabolic status involving a mechanism reliant upon release of the type 2 initiator cytokine IL-33. IL-33 initiates the accumulation of group 2 innate lymphoid cells (ILC2s), eosinophils, and alternatively activated macrophages in the adipose tissue. IL-33 release from cells in the adipose tissue is mediated by the RNase activity of ω1; however, the ability of ω1 to improve metabolic status is reliant upon effective binding of ω1 to CD206. We demonstrate a novel mechanism for RNase-mediated release of IL-33 inducing ILC2-dependent improvements in the metabolic status of obese animals.

Keywords: adipocytes; inflammation; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / immunology*
  • Egg Proteins / immunology*
  • Eosinophils / immunology
  • Helminth Proteins / immunology*
  • Immunity, Innate*
  • Interleukin-33 / genetics
  • Interleukin-33 / immunology*
  • Lectins, C-Type / immunology
  • Lymphocytes / immunology*
  • Macrophage Activation / genetics
  • Macrophages / immunology
  • Mannose Receptor
  • Mannose-Binding Lectins / immunology
  • Mice
  • Mice, Knockout
  • Mice, Obese
  • Obesity / genetics
  • Obesity / immunology
  • Receptors, Cell Surface / immunology
  • Ribonucleases / immunology*
  • Schistosoma mansoni / enzymology
  • Schistosoma mansoni / immunology*

Substances

  • Antigens, Helminth
  • Egg Proteins
  • Helminth Proteins
  • Il33 protein, mouse
  • Interleukin-33
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • omega-1 antigen, Schistosoma mansoni
  • Ribonucleases