A LIAISON BETWEEN THE IMMUNE AND METABOLIC SYSTEMS: FAT REGULATORY T CELLS
CIPOLLETTA, DANIELA (2010) A LIAISON BETWEEN THE IMMUNE AND METABOLIC SYSTEMS: FAT REGULATORY T CELLS. [Tesi di dottorato] (Inedito)
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Obesity is characterized by low-grade inflammation of adipose tissue, which promotes insulin resistance and type-2 diabetes. Previous studies have highlighted the role of inflammatory macrophages in the onset of insulin resistance secondary to obesity. Here we explored the role of other players of the immune system in fat inflammation that normally are responsible for guarding against run-away auto-immunity, T regulatory cells. Regulatory CD4+ T cells that express the transcription factor Foxp3 (termed Tregs) are a lymphocyte lineage specialized in controlling immune responses. We report that Tregs with a unique phenotype are highly enriched in the abdominal fat of normal mice, but are strikingly and specifically reduced in insulin-resistant models of obesity. Loss-of-function and gain-of-function experiments demonstrated that Tregs regulate the inflammatory state of adipose tissue as well as insulin resistance. Cytokines differentially synthesized by fat-resident regulatory and conventional T cells directly impacted the synthesis of inflammatory mediators and glucose uptake by cultured adipocytes. In summary, we described a population of tissue specialized Treg cells that may modulate neighboring cells in potentially pathological contexts, which opens the door to harnessing their anti-inflammatory properties to inhibit elements of the metabolic syndrome.
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