Article abstract
Nature Medicine 15, 930 - 939 (2009)
Published online: 26 July 2009 | doi:10.1038/nm.2002
Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters
Markus Feuerer1,5, Laura Herrero2,5, Daniela Cipolletta1,4,5, Afia Naaz2, Jamie Wong1,5, Ali Nayer2, Jongsoon Lee2, Allison B Goldfine3, Christophe Benoist1,5, Steven Shoelson2 & Diane Mathis1,5
Abstract
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.
- Immunology and Immunogenetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- Cellular and Molecular Physiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- Clinical Research, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- European School of Molecular Medicine, Naples, Italy.
- Present addresses: Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA (M.F., D.C., C.B. and D.M.); Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Barcelona, Spain (L.H.); Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA (J.W.).
Correspondence to: Diane Mathis1,5 e-mail: dm@hms.harvard.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
T reg cells: guardians for lifeNature Immunology News and Views (01 Feb 2007)
T-ing up inflammation in fatNature Medicine News and Views (01 Aug 2009)
See all 3 matches for News And ViewsRESEARCH
Diagnostic Ionizing Radiation Exposure in a Population-Based Sample of Children With Inflammatory Bowel DiseasesThe American Journal of Gastroenterology Article Response
Normalization of obesity-associated insulin resistance through immunotherapyNature Medicine Article (01 Aug 2009)
See all 46 matches for Research
