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KLF10 Deficiency in CD4+ T Cells Triggers Obesity, Insulin Resistance, and Fatty Liver.


ABSTRACT: CD4+ T cells regulate inflammation and metabolism in obesity. An imbalance of CD4+ T regulatory cells (Tregs) is critical in the development of insulin resistance and diabetes. Although cytokine control of this process is well understood, transcriptional regulation is not. KLF10, a member of the Kruppel-like transcription factor family, is an emerging regulator of immune cell function. We generated CD4+-T-cell-specific KLF10 knockout (TKO) mice and identified a predisposition to obesity, insulin resistance, and fatty liver due to defects of CD4+ Treg mobilization to liver and adipose tissue depots and decreased transforming growth factor ?3 (TGF-?3) release in vitro and in vivo. Adoptive transfer of wild-type CD4+ Tregs fully rescued obesity, insulin resistance, and fatty liver. Mechanistically, TKO Tregs exhibit reduced mitochondrial respiration and glycolysis, phosphatidylinositol 3-kinase (PI3K)-Akt-mTOR signaling, and consequently impaired chemotactic properties. Collectively, our study identifies CD4+ T cell KLF10 as an essential regulator of obesity and insulin resistance by altering Treg metabolism and mobilization.

SUBMITTER: Wara AK 

PROVIDER: S-EPMC7816773 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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CD4<sup>+</sup> T cells regulate inflammation and metabolism in obesity. An imbalance of CD4<sup>+</sup> T regulatory cells (Tregs) is critical in the development of insulin resistance and diabetes. Although cytokine control of this process is well understood, transcriptional regulation is not. KLF10, a member of the Kruppel-like transcription factor family, is an emerging regulator of immune cell function. We generated CD4<sup>+</sup>-T-cell-specific KLF10 knockout (TKO) mice and identified a p  ...[more]

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