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

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 sta...

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Bibliographic Details
Published in:The FASEB journal 2016-02, Vol.30 (2), p.824-835
Main Authors: Hams, Emily, Bermingham, Rachel, Wurlod, Felicity A., Hogan, Andrew E., O'Shea, Donal, Preston, Roger J., Rodewald, Hans‐Reimer, McKenzie, Andrew N. J., Fallon, Padraic G.
Format: Article
Language:English
Subjects:
adipocytes
Animals
Antigens, Helminth - immunology
Egg Proteins - immunology
Eosinophils - immunology
Helminth Proteins - immunology
Immunity, Innate
inflammation
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
Obesity - genetics
Obesity - immunology
Receptors, Cell Surface - immunology
Research Communication
Ribonucleases - immunology
Schistosoma mansoni - enzymology
Schistosoma mansoni - immunology
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Summary: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.—Hams, E., Bermingham, R., Wurlod, F. A., Hogan, A. E., O'Shea, D., Preston, R. J., Rodewald, H.‐R., McKenzie, A. N. J., Fallon, P. G. The helminth T2 RNase ω1 promotes metabolic homeostasis in an IL‐33‐ and group 2 innate lymphoid cell‐dependent mechanism. FASEB J. 30, 824–835 (2016). www.fasebj.org
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.15-277822