title: IL-33 Reverses an Obesity-Induced Deficit in Visceral Adipose Tissue ST2+ T Regulatory Cells and Ameliorates Adipose Tissue Inflammation and Insulin Resistance.
abstract: Obesity is associated with insulin resistance and inflammation thought to be caused by a visceral adipose tissue (VAT)-localized reduction in immunoregulatory cells and increase in proinflammatory immune cells. We previously found that VAT regulatory T cells (Tregs) normally express high levels of IL-10 and that expression of this cytokine in VAT Tregs is specifically reduced in mice fed a high-fat diet. In this study, we further investigated the phenotype of VAT Tregs and found that the majority of IL-10-expressing Tregs in the VAT of lean mice also expressed the ST2 chain of the IL-33R. In addition to high expression of IL-10, ST2(+) Tregs in lean VAT expressed higher proportions of Th2-associated proteins, including GATA3 and CCR4, and Neuropillin-1 compared with ST2(-) Tregs. The proportion of ST2(+) Tregs in VAT was severely diminished in obese mice that had been fed a high-fat/sucrose diet, and this effect could be completely reversed by treatment with IL-33. IL-33 treatment also reversed VAT inflammation in obese mice and resulted in a reduction of hyperinsulinemia and insulin resistance. These data suggest that IL-33 contributes to the maintenance of the normal pool of ST2(+) Tregs in the VAT, and that therapeutic administration of IL-33 results in multiple anti-obesity effects, including the reversal of VAT inflammation and alleviation of insulin resistance.
authors: Department of Surgery, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.
authors: Jonathan M
authors: JM
authors: Han
authors: Department of Surgery, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.
authors: Dan
authors: D
authors: Wu
authors: Department of Surgery, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.
authors: Heather C
authors: HC
authors: Denroche
authors: Department of Surgery, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.
authors: Yu
authors: Y
authors: Yao
authors: Department of Surgery, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.
authors: C Bruce
authors: CB
authors: Verchere
authors: Department of Surgery, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada mlevings@mail.ubc.ca.
authors: Megan K
authors: MK
authors: Levings
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology; D007333:Insulin Resistance / Q000276:immunology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology*; D050152:Intra-Abdominal Fat / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000276:immunology*; D018123:Receptors, Interleukin / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin