Image_2_A Novel Role for Triglyceride Metabolism in Foxp3 Expression.pdf
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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References
- https://doi.org//10.3389/fimmu.2017.01949
- https://doi.org//10.4049/jimmunol.1003613
- https://doi.org//10.1172/jci.insight.89160
- https://doi.org//10.1038/nm.3704
- https://doi.org//10.1016/j.immuni.2017.08.005
- https://doi.org//10.1134/S0006297908030097
- https://doi.org//10.1189/jlb.1111537
- https://doi.org//10.1146/annurev-pathol-011110-130138
- https://doi.org//10.1016/j.bbalip.2016.09.002
- https://doi.org//10.1016/j.devcel.2017.06.003
- https://doi.org//10.1111/j.1742-4658.2010.07972.x
- https://doi.org//10.1080/15548627.2016.1235123
- https://doi.org//10.1016/j.cmet.2017.07.012
- https://doi.org//10.1073/pnas.0630588100
- https://doi.org//10.1194/jlr.M033365
- https://doi.org//10.1038/nm.2439
- https://doi.org//10.1073/pnas.0911679106
- https://doi.org//10.1038/nm.2238
- https://doi.org//10.1074/jbc.M112.434910
- https://doi.org//10.1016/j.immuni.2014.06.005
- https://doi.org//10.1016/j.tem.2011.04.002
- https://doi.org//10.1016/j.abb.2018.08.001
- https://doi.org//10.1111/j.1440-1746.2009.05823.x
- https://doi.org//10.1084/jem.20110767
- https://doi.org//10.1084/jem.20040179
- https://doi.org//10.1016/j.immuni.2008.03.018
- https://doi.org//10.1194/jlr.R800018-JLR200
- https://doi.org//10.1093/bioinformatics/bty528
- https://doi.org//10.1093/nar/gkw253
- https://doi.org//10.1016/j.cub.2015.04.004
- https://doi.org//10.1097/00041433-200410000-00007
- https://doi.org//10.1074/jbc.M305760200
- https://doi.org//10.1038/ni.3365
- https://doi.org//10.1073/pnas.1011859107
- https://doi.org//10.1016/j.cell.2015.10.068
- https://doi.org//10.4049/jimmunol.1002361
- https://doi.org//10.1016/j.immuni.2009.09.022
- https://doi.org//10.4049/jimmunol.1200449
- https://doi.org//10.1371/journal.pbio.0060276
- https://doi.org//10.1093/nar/29.9.e45
- https://doi.org//10.1016/j.talanta.2017.01.003
- https://doi.org//10.1021/ac3029745
- https://doi.org//10.1021/ac300698c
- https://doi.org//10.1073/pnas.1817669116
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Categories
- Transplantation Immunology
- Tumour Immunology
- Immunology not elsewhere classified
- Immunology
- Veterinary Immunology
- Animal Immunology
- Genetic Immunology
- Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
- Autoimmunity
- Cellular Immunology
- Humoural Immunology and Immunochemistry
- Immunogenetics (incl. Genetic Immunology)
- Innate Immunity