Visceral adipose tissues (VATs) have a distinct subset of Treg cells. In Nature, Mathis and colleagues show that the transcription factor PPAR-γ is required for the unique gene-expression profile and functions of VAT Treg cells relative to those of lymph node Treg cells. Retroviral expression of PPAR-γ1 or PPAR-γ2 with Foxp3 recapitulates much of the VAT Treg cell expression profile, which differs from that induced by Foxp3 alone and includes upregulation of genes encoding molecules linked to lipid metabolism; however, PPAR-γ1 has additional inhibitory functions not seen with PPAR-γ2. Ppargf/f × Foxp3-Cre mice, which experience conditional loss of PPAR-γ, have fewer VAT Treg cells and have altered leukocyte populations in visceral fat. These mice likewise develop metabolic syndrome. PPAR-γ expression by fat Treg cells is necessary for the effective restoration of insulin sensitivity by thiazolidinedione, a drug used for the treatment of type II diabetes. These findings suggest that tissue-specific Treg cells manifest distinct functions.

Nature (16 May 2012) doi:10.1038/nature11132