title: Cutting edge: IL-25 elicits innate lymphoid type 2 and type II NKT cells that regulate obesity in mice.
abstract: The cellular composition of visceral adipose tissue (VAT) and release of cytokines by such cells within VAT has been implicated in regulating obesity and metabolic homeostasis. We show the importance of IL-25-responsive innate cells, which release the Th2 cytokine IL-13, in regulating weight and glucose homeostasis in mouse models of diet-induced obesity. Treating obese mice with IL-25 induces weight loss and improves glucose tolerance, and is associated with increased infiltration of innate lymphoid type 2 cells (ILC2), type I and type II NKT cells, eosinophils, and alternatively activated macrophages into the VAT. By depleting ILC2 in obese Rag1(-/-) mice, we observe exacerbated weight gain and glucose intolerance. Conversely, transferring ILC2 or type I or type II NKT cells into obese mice induces transient weight loss and stabilizes glucose homeostasis. Our data identify a mechanism whereby IL-25 eliciting IL-13-producing innate cells regulates inflammation in adipose tissue and prevents diet-induced obesity.
authors.affiliation: Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin 2, Ireland;
authors.forename: Emily
authors.initials: E
authors.lastname: Hams
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement; D005947:Glucose / Q000276:immunology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D006706:Homeostasis; D007113:Immunity, Innate; D056747:Immunomodulation; D018793:Interleukin-13 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D050152:Intra-Abdominal Fat / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D009765:Obesity / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D018398:Homeodomain Proteins; D018793:Interleukin-13; D007378:Interleukins; C442281:Mydgf protein, mouse; C064658:RAG-1 protein; D005947:Glucose