Adipose tissue-resident regulatory T cells: phenotypic specialization, functions and therapeutic potential.

Foxp3(+)  CD4(+) regulatory T (Treg) cells, recognized to be one of the most important defences of the human body against an inappropriate immune response, have recently gained attention from those outside immunology thanks to the compelling evidence for their capability to exert non-canonical immune functions in a variety of tissues in health and disease. The recent discovery of the differences between tissue-resident Treg cells and those derived from lymphoid organs is affecting the mindset of many investigators now questioning the broad applicability of observations originally based on peripheral blood/lymphoid organ cells. So far, the best characterized 'Treg flavour' comes from studies focused on their role in suppressing adipose tissue inflammation and obesity-driven insulin resistance. Adipose tissue derived Treg cells are distinct from their counterparts in lymphoid organs based on their transcriptional profile, T-cell receptor repertoire, and cytokine and chemokine receptor expression pattern. These cells are abundant in visceral adipose tissue of lean mice but their number is greatly reduced in insulin-resistant animal models of obesity. Interestingly, peroxisome-proliferator-activated receptor γ expression by visceral adipose tissue Treg cells is crucial for their accumulation, phenotype and function in the fat and surprisingly necessary for complete restoration of insulin sensitivity in obese mice by the anti-diabetic drug Pioglitazone. This review surveys recent findings relating to the unique phenotype and function of adipose tissue-resident Treg cells, speculates on the nature of their dynamics in lean and obese mouse models, and analyses their potential therapeutic application in the treatment of type 2 diabetes.