Appearance and disappearance of the mRNA signature characteristic of Treg cells in visceral adipose tissue: Age, diet, and PPARγ effects

A unique population of Foxp3(+)CD4(+) regulatory T (T-reg) cells resides in visceral adipose tissue (VAT) of lean mice, especially in the epididymal fat depot. VAT T-regs are unusual in their very high representation within the CD4(+) T-cell compartment, their transcriptome, and their repertoire of antigen-specific T-cell receptors. They are important regulators of local and systemic inflammation and metabolism. The overall goal of this study was to learn how the VAT T-reg transcriptome adapts to different stimuli; in particular, its response to aging in lean mice, to metabolic perturbations associated with obesity, and to certain signaling events routed through PPAR gamma, the "master-regulator" of adipocyte differentiation. We show that the VAT T-reg signature is imposed early in life, well before age-dependent expansion of the adipose-tissue Treg population. VAT T-regs in obese mice lose the signature typical of lean individuals but gain an additional set of over-and underrepresented transcripts. This obese mouse VAT T-reg signature depends on phosphorylation of the serine residue at position 273 of PPAR gamma, in striking parallel to a pathway recently elucidated in adipocytes. These findings are important to consider in designing drugs to target type 2 diabetes and other features of the "metabolic syndrome."