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PMID: 20445103 Published · ppublish English Journal Article

Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob/ob mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 21 ·2010-05-25 ·Pages 9765-70

Ilan Y, Maron R, Tukpah AM, Maioli TU, Murugaiyan G, Yang K, Wu HY, Weiner HL

Abstract

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.

MeSH Terms
Adipose Tissue/immunology Animals Blood Glucose/metabolism Cell Proliferation Cholesterol/blood Diabetes Mellitus, Type 2/blood,immunology Hyperplasia/immunology Inflammation/immunology Insulin Resistance Liver/enzymology Mice Mice, Inbred C57BL Mice, Obese Natural Killer T-Cells/immunology Pancreas/immunology T-Lymphocytes, Regulatory/cytology,immunology
Chemicals
Blood Glucose Cholesterol
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Ilan Yaron
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Maron Ruth
Tukpah Ann-Marcia
Maioli Tatiani Uceli
Murugaiyan Gopal
Yang Kaiyong
Wu Henry Yim
Weiner Howard L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0908771107
Published
2010-05-25
Epub
2010-00-05
Pages
9765-70
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2906892
Subset
IM
Grants
NIAID NIH HHS · R01 AI043458 · United States
NIAID NIH HHS · R01 AI043458-09 · United States
External Links
PubMed source DOI: 10.1073/pnas.0908771107 PMC Full Text View journal details
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