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.
*Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland; Obesity Immunology, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland; Department of Endocrinology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland; Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany; and Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Emily
E
Hams
*Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland; Obesity Immunology, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland; Department of Endocrinology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland; Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany; and Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Rachel
R
Bermingham
*Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland; Obesity Immunology, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland; Department of Endocrinology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland; Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany; and Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Felicity A
FA
Wurlod
*Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland; Obesity Immunology, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland; Department of Endocrinology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland; Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany; and Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Andrew E
AE
Hogan
*Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland; Obesity Immunology, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland; Department of Endocrinology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland; Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany; and Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Donal
D
O'Shea
*Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland; Obesity Immunology, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland; Department of Endocrinology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland; Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany; and Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Roger J
RJ
Preston
*Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland; Obesity Immunology, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland; Department of Endocrinology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland; Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany; and Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Hans-Reimer
HR
Rodewald
*Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland; Obesity Immunology, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland; Department of Endocrinology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland; Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany; and Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Andrew N J
AN
McKenzie
*Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland; Obesity Immunology, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland; Department of Endocrinology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland; Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany; and Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom pfallon@tcd.ie.
Padraic G
PG
Fallon
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D004527:Egg Proteins / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D015801:Helminth Proteins / Q000276:immunology*; D007113:Immunity, Innate; D000067596:Interleukin-33 / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008262:Macrophage Activation / Q000235:genetics; D008264:Macrophages / Q000276:immunology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology; D012260:Ribonucleases / Q000276:immunology*; D012550:Schistosoma mansoni / Q000201:enzymology / Q000276:immunology*
D000947:Antigens, Helminth; D004527:Egg Proteins; D015801:Helminth Proteins; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; C587622:omega-1 antigen, Schistosoma mansoni; D012260:Ribonucleases
adipocytes; inflammation; obesity