Dataset Information

A Novel Role for Triglyceride Metabolism in Foxp3 Expression.

ABSTRACT: Lipid metabolism plays a key role in many cellular processes. We show here that regulatory T cells have enhanced lipid storage within subcellular lipid droplets (LD). They also express elevated amounts of both isoforms of diacylglycerol acyl transferase (DGAT1 & 2), enzymes required for the terminal step of triacylglycerol synthesis. In regulatory T-cells (Tregs), the conversion of diacylglycerols to triacylglycerols serves two additional purposes other than lipid storage. First, we demonstrate that it protects T cells from the toxic effects of saturated long chain fatty acids. Second, we show that Triglyceride formation is essential for limiting activation of protein kinase C via free diacyl glycerol moieties. Inhibition of DGAT1 resulted in elevated active PKC and nuclear NFKB, as well as impaired Foxp3 induction in response to TGF?. Thus, Tregs utilize a positive feedback mechanism to promote sustained expression of Foxp3 associated with control of LD formation.

SUBMITTER: Howie D

PROVIDER: S-EPMC6701200 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Novel Role for Triglyceride Metabolism in Foxp3 Expression.

Howie Duncan D Ten Bokum Annemieke A Cobbold Stephen Paul SP Yu Zhanru Z Kessler Benedikt M BM Waldmann Herman H

Frontiers in immunology 20190813

Lipid metabolism plays a key role in many cellular processes. We show here that regulatory T cells have enhanced lipid storage within subcellular lipid droplets (LD). They also express elevated amounts of both isoforms of diacylglycerol acyl transferase (DGAT1 & 2), enzymes required for the terminal step of triacylglycerol synthesis. In regulatory T-cells (Tregs), the conversion of diacylglycerols to triacylglycerols serves two additional purposes other than lipid storage. First, we demonstrate ...[more]

PMID: 31456800

Similar Datasets

Project description:BackgroundGrowing evidence has proved that Forkhead box protein 3 (FOXP3), which is a master regulatory gene in the development and function of regulatory T-cells, is expressed in human cancer cells. This expression indicates the crucial role FOXP3 takes up as the disease progresses. However, its role in colorectal cancer (CRC) liver metastasis is still mostly unknown. This study set out to explore the molecular characteristics of FOXP3 in driving the liver metastasis within CRC.MethodsWe downloaded the RNA-seq data from the GSE50760. Weighted gene co-expression network analysis (WGCNA)WGCNA and RNA-Seq analysis were applied to find the key gene network associated with colorectal cancer liver metastasis. Then we performed pathway enrichment analysis on liver metastasis-associated gene set. Immunohistochemistry, in vitro and in vivo studies were conducted to test expression and function of FOXP3 in CRC tissues and liver metastasis tissues. Non-targeted metabolomics analysis was performed to identify the alteration of FOXP3 expression in metabolites of colorectal cancer liver metastasis. Western blot was performed to confirm changes of matrix metalloproteinase 9MMP9 expression were downstream events of S-adenosyl-methionine (SAM).ResultsWe found that FOXP3 and MMP9 exhibited co-expression relationships and affected liver metastasis in CRC. Upregulation of FOXP3 promotes cell migration and invasion in CRC, which suggests a pro-cancer effect. Moreover, metabolomics analysis showed that knockdown of FOXP3 significantly reduced SAM levels, and changes of MMP9 expression were downstream events of SAM, which is concentration-dependent. Besides, The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Western blot analysis confirmed that overexpression of FOXP3 activates the Wnt pathway to promote colon cancer metastasis.ConclusionsOur results altogether suggested that FOXP3 expression inhibited the SAM cycle to reduce SAMe levels, resulting in altered MMP9 expression and helped CRC liver metastasis.

Dataset Information

A Novel Role for Triglyceride Metabolism in Foxp3 Expression.

Publications

A Novel Role for Triglyceride Metabolism in Foxp3 Expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets