Obesity is accompanied by chronic, low-grade inflammation of adipose tissue, which promotes insulin resistance and type-2 diabetes. These findings raise the question of how fat inflammation can escape the powerful armamentarium of cells and molecules normally responsible for guarding against a runaway immune response. CD4+ Foxp3+ T regulatory (Treg) cells with a unique phenotype were highly enriched in the abdominal fat of normal mice, but their numbers were strikingly and specifically reduced at this site in insulin-resistant models of obesity. Loss-of-function and gain-of-function experiments revealed that these Treg cells influenced the inflammatory state of adipose tissue and, thus, insulin resistance. Cytokines differentially synthesized by fat-resident regulatory and conventional T cells directly affected the synthesis of inflammatory mediators and glucose uptake by cultured adipocytes. These observations suggest that harnessing the anti-inflammatory properties of Treg cells to inhibit elements of the metabolic syndrome may have therapeutic potential.
Markus Feuerer, Laura Herrero, Daniela Cipolletta, Afia Naaz, Jamie Wong, Ali Nayer, Jongsoon Lee, Allison B Goldfine, Christophe Benoist, Steven Shoelson & Diane Mathis. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nature Medicine 2009 July 1.Immunology and Immunogenetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.