NDLI: IL-33 Reverses an Obesity-Induced Deficit in Visceral Adipose Tissue ST2+ T Regulatory Cells and Ameliorates Adipose Tissue Inflammation and Insulin Resistance.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Levings, Megan K. Verchere, C. Bruce Denroche, Heather C. Han, Jonathan M. Yao, Yu Wu, Dan
Description	Country affiliation: Canada Author Affiliation: Han JM ( Department of Surgery, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.); Wu D ( Department of Surgery, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.); Denroche HC ( Department of Surgery, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.); Yao Y ( Department of Surgery, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.); Verchere CB ( Department of Surgery, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.); Levings MK ( Department of Surgery, University of British Columbia and Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada mlevings@mail.ubc.ca.)
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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	10
Volume Number	194
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-05-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Insulin Resistance Interleukins Immunology Intra-abdominal Fat Obesity T-lymphocyte Subsets T-lymphocytes, Regulatory Animals Diet, High-fat Adverse Effects Flow Cytometry Inflammation Interleukin-33 Mice Mice, Inbred C57bl Receptors, Interleukin Reverse Transcriptase Polymerase Chain Reaction Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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