| Literature DB >> 30043753 |
Brenda Raud1, Dominic G Roy2, Ajit S Divakaruni3, Tatyana N Tarasenko4, Raimo Franke5, Eric H Ma2, Bozena Samborska2, Wei Yuan Hsieh6, Alison H Wong2, Philipp Stüve1, Catharina Arnold-Schrauf1, Melanie Guderian1, Matthias Lochner1, Shakuntala Rampertaap7, Kimberly Romito7, Joseph Monsale7, Mark Brönstrup5, Steven J Bensinger8, Anne N Murphy9, Peter J McGuire4, Russell G Jones10, Tim Sparwasser11, Luciana Berod12.
Abstract
T cell subsets including effector (Teff), regulatory (Treg), and memory (Tmem) cells are characterized by distinct metabolic profiles that influence their differentiation and function. Previous research suggests that engagement of long-chain fatty acid oxidation (LC-FAO) supports Foxp3+ Treg cell and Tmem cell survival. However, evidence for this is mostly based on inhibition of Cpt1a, the rate-limiting enzyme for LC-FAO, with the drug etomoxir. Using genetic models to target Cpt1a specifically in T cells, we dissected the role of LC-FAO in primary, memory, and regulatory T cell responses. Here we show that the ACC2/Cpt1a axis is largely dispensable for Teff, Tmem, or Treg cell formation, and that the effects of etomoxir on T cell differentiation and function are independent of Cpt1a expression. Together our data argue that metabolic pathways other than LC-FAO fuel Tmem or Treg differentiation and suggest alternative mechanisms for the effects of etomoxir that involve mitochondrial respiration.Entities:
Keywords: AMPK; CD8 T cells; CPT; acetyl-CoA carboxylase; carnitine palmitoyltransferase; etomoxir; fatty acid oxidation; memory T cells; regulatory T cells
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Year: 2018 PMID： 30043753 PMCID： PMC6747686 DOI： 10.1016/j.cmet.2018.06.002
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287