Adipose tissue regulatory T cells: differentiation and function

Rising obesity levels, worldwide, are resulting in substantial increases in cardiovascular disease, diabetes, kidney disease, musculoskeletal disorders, and certain cancers, and obesity-associated illnesses are estimated to cause ∼4 million deaths worldwide per year. A common theme in this disease epidemic is the chronic systemic inflammation that accompanies obesity. CD4⁺ Foxp3⁺ regulatory T cells residing in visceral adipose tissues (VAT Tregs) are a unique immune cell population that play essential functions in restricting obesity-associated systemic inflammation through regulation of adipose tissue homeostasis. The distinct transcriptional program that defines VAT Tregs has been described, but directly linking VAT Treg differentiation and function to improving insulin sensitivity has proven more complex. Here we review new findings which have clarified how VAT Tregs differentiate, and how distinct VAT Treg subsets regulate VAT homeostasis, energy expenditure, and insulin sensitivity.