IL-33 reverses an obesity-induced deficit in visceral adipose tissue ST2+ T regulatory cells and ameliorates adipose tissue inflammation and insulin resistance

JM Han, D Wu, HC Denroche, Y Yao… - The Journal of …, 2015 - journals.aai.org
The Journal of Immunology, 2015journals.aai.org
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 …
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.
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