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Details

Autor(en) / Beteiligte
Titel
Insulin inhibits IL-10-mediated regulatory T cell function: implications for obesity
Ist Teil von
  • The Journal of immunology (1950), 2014-01, Vol.192 (2), p.623-629
Ort / Verlag
United States: The American Association of Immunologists
Erscheinungsjahr
2014
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
  • Chronic inflammation is known to promote metabolic dysregulation in obesity and type 2 diabetes. Although the precise origin of the unchecked inflammatory response in obesity is unclear, it is known that overproduction of proinflammatory cytokines by innate immune cells affects metabolism. For example, TNF-α contributes to the inability of cells to respond to insulin and to the increase in levels of insulin. Whether this hyperinsulinemia itself is part of a feedback loop that affects the progression of chronic adipose inflammation is unknown. In this article, we show that regulatory T cells (Tregs) express the insulin receptor, and that high levels of insulin impair the ability of Tregs to suppress inflammatory responses via effects on the AKT/mTOR signaling pathway. Insulin activated AKT signaling in Tregs, leading to inhibition of both IL-10 production and the ability of Tregs to suppress the production of TNF-α by macrophages in a contact-independent manner. The effect of insulin on Treg suppression was limited to IL-10 production and it did not alter the expression of other proteins associated with Treg function, including CTLA-4, CD39, and TGF-β. In a model of diet-induced obesity, Tregs from the visceral adipose tissue of hyperinsulinemic, obese mice showed a similar specific decrease in IL-10 production, as well as a parallel increase in production of IFN-γ. These data suggest that hyperinsulinemia may contribute to the development of obesity-associated inflammation via a previously unknown effect of insulin on the IL-10-mediated function of Tregs.
Sprache
Englisch
Identifikatoren
ISSN: 0022-1767
eISSN: 1550-6606
DOI: 10.4049/jimmunol.1302181
Titel-ID: cdi_proquest_miscellaneous_1490750911
Format
Schlagworte
Animals, Antigens, CD - immunology, Antigens, CD - metabolism, Apyrase - immunology, Apyrase - metabolism, Cells, Cultured, CTLA-4 Antigen - immunology, CTLA-4 Antigen - metabolism, Endocrinology, Epithelial Cells - immunology, Epithelial Cells - metabolism, Epithelium - immunology, Epithelium - metabolism, Hyperinsulinemia, Hyperinsulinism - immunology, Hyperinsulinism - metabolism, Immunology, Inflammation, Inflammation - immunology, Inflammation - metabolism, Insulin, Insulin - immunology, Insulin - metabolism, Insulin receptor, Interferon-gamma - immunology, Interferon-gamma - metabolism, Interleukin 10, Interleukin-10 - antagonists & inhibitors, Interleukin-10 - immunology, Interleukin-10 - metabolism, Internal medicine, Intra-Abdominal Fat - immunology, Intra-Abdominal Fat - metabolism, Macrophages - immunology, Macrophages - metabolism, Mice, Mice, Inbred C57BL, Obesity - immunology, Obesity - metabolism, Proinflammatory cytokine, Protein kinase B, Proto-Oncogene Proteins c-akt - immunology, Proto-Oncogene Proteins c-akt - metabolism, Receptor, Insulin - immunology, Receptor, Insulin - metabolism, Regulatory T cell, Signal Transduction - immunology, T-Lymphocytes, Regulatory - immunology, T-Lymphocytes, Regulatory - metabolism, TOR Serine-Threonine Kinases - immunology, TOR Serine-Threonine Kinases - metabolism, Transforming Growth Factor beta - immunology, Transforming Growth Factor beta - metabolism, Tumor Necrosis Factor-alpha - immunology, Tumor Necrosis Factor-alpha - metabolism

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