%A Howie,Duncan %A Ten Bokum,Annemieke %A Cobbold,Stephen Paul %A Yu,Zhanru %A Kessler,Benedikt M. %A Waldmann,Herman %D 2019 %J Frontiers in Immunology %C %F %G English %K Regulatory T (Treg) cell,tolerance,Metabolism,differentiation,lipotoxicity,Metabolomics %Q %R 10.3389/fimmu.2019.01860 %W %L %M %P %7 %8 2019-August-13 %9 Original Research %# %! Lipid droplets in Treg %* %< %T A Novel Role for Triglyceride Metabolism in Foxp3 Expression %U https://www.frontiersin.org/articles/10.3389/fimmu.2019.01860 %V 10 %0 JOURNAL ARTICLE %@ 1664-3224 %X 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.