Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters.
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 (T(reg)) 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 T(reg) 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 T(reg) cells to inhibit elements of the metabolic syndrome may have therapeutic potential.
Feuerer
Markus
M
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts, USA.
Herrero
Laura
L
Cipolletta
Daniela
D
Naaz
Afia
A
Wong
Jamie
J
Nayer
Ali
A
Lee
Jongsoon
J
Goldfine
Allison B
AB
Benoist
Christophe
C
Shoelson
Steven
S
Mathis
Diane
D
D000273:Adipose Tissue / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D049109:Cell Proliferation; D002469:Cell Separation; D020869:Gene Expression Profiling; D018655:Lymphocyte Count; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000473:pathology / Q000502:physiology*; D013851:Thinness / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology