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 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