Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 21, Pages 9765-9770Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0908771107
Keywords
adipocytes; oral anti-CD3; type II diabetes; inflammation
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Funding
- NIAID NIH HHS [R01 AI043458, R01 AI043458-09] Funding Source: Medline
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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 CD(4+)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.
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