[HTML][HTML] A novel role for triglyceride metabolism in Foxp3 expression

D Howie, A Ten Bokum, SP Cobbold, Z Yu… - Frontiers in …, 2019 - frontiersin.org
Frontiers in immunology, 2019frontiersin.org
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 …
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 TGFβ. Thus, Tregs utilize a positive feedback mechanism to promote sustained expression of Foxp3 associated with control of LD formation.
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