Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob/ob mice.
Leptin-deficient ob/ob mice are overweight, develop insulin resistance, and serve as a model for type 2 diabetes (T2D). Studies suggest that inflammatory pathways are linked to the development of insulin resistance and T2D both in animals and humans. We asked whether the induction of regulatory T cells (Tregs) could alleviate the pathological and metabolic abnormalities in ob/ob mice. We induced TGF-beta-dependent CD4(+) latency-associated peptide (LAP)-positive Tregs by oral administration of anti-CD3 antibody plus beta-glucosylceramide. We found a decrease in pancreatic islet cell hyperplasia, fat accumulation in the liver, and inflammation in adipose tissue, accompanied by lower blood glucose and liver enzymes. In addition, treated animals had decreased CD11b(+)F4/80(+) macrophages and TNF-alpha in adipose tissue. Adoptive transfer of orally induced CD4(+)LAP(+) Tregs ameliorated metabolic and cytokine abnormalities. Our results demonstrate the importance of inflammation in T2D and identify a unique immunological approach for treatment of T2D by the induction of Tregs.
Ilan
Yaron
Y
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Maron
Ruth
R
Tukpah
Ann-Marcia
AM
Maioli
Tatiani Uceli
TU
Murugaiyan
Gopal
G
Yang
Kaiyong
K
Wu
Henry Yim
HY
Weiner
Howard L
HL
D000273:Adipose Tissue / Q000276:immunology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology; D006965:Hyperplasia / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D055611:Natural Killer T-Cells / Q000276:immunology; D010179:Pancreas / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D001786:Blood Glucose; D002784:Cholesterol
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