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Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation.
Raud, Brenda; Roy, Dominic G; Divakaruni, Ajit S; Tarasenko, Tatyana N; Franke, Raimo; Ma, Eric H; Samborska, Bozena; Hsieh, Wei Yuan; Wong, Alison H; Stüve, Philipp; Arnold-Schrauf, Catharina; Guderian, Melanie; Lochner, Matthias; Rampertaap, Shakuntala; Romito, Kimberly; Monsale, Joseph; Brönstrup, Mark; Bensinger, Steven J; Murphy, Anne N; McGuire, Peter J; Jones, Russell G; Sparwasser, Tim; Berod, Luciana.
Afiliação
  • Raud B; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Niedersachsen 30625, Germany.
  • Roy DG; Goodman Cancer Research Centre, Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada.
  • Divakaruni AS; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Tarasenko TN; Metabolism, Infection, and Immunity Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Franke R; Department of Chemical Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
  • Ma EH; Goodman Cancer Research Centre, Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada.
  • Samborska B; Goodman Cancer Research Centre, Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada.
  • Hsieh WY; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wong AH; Goodman Cancer Research Centre, Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada.
  • Stüve P; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Niedersachsen 30625, Germany.
  • Arnold-Schrauf C; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Niedersachsen 30625, Germany.
  • Guderian M; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Niedersachsen 30625, Germany.
  • Lochner M; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Niedersachsen 30625, Germany.
  • Rampertaap S; Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, USA.
  • Romito K; Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, USA.
  • Monsale J; Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, USA.
  • Brönstrup M; Department of Chemical Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
  • Bensinger SJ; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, C
  • Murphy AN; Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
  • McGuire PJ; Metabolism, Infection, and Immunity Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Jones RG; Goodman Cancer Research Centre, Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada. Electronic address: russell.jones@mcgill.ca.
  • Sparwasser T; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Niedersachsen 30625, Germany. Electronic address: sparwasser.tim@mh-hannove
  • Berod L; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Niedersachsen 30625, Germany. Electronic address: luciana.berod@twincore.de
Cell Metab ; 28(3): 504-515.e7, 2018 09 04.
Article em En | MEDLINE | ID: mdl-30043753
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Acetil-CoA Carboxilase / Carnitina O-Palmitoiltransferase / Linfócitos T Reguladores / Linfócitos T CD8-Positivos / Compostos de Epóxi / Ácidos Graxos / Memória Imunológica / Mitocôndrias Limite: Animals / Child / Child, preschool / Female / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Acetil-CoA Carboxilase / Carnitina O-Palmitoiltransferase / Linfócitos T Reguladores / Linfócitos T CD8-Positivos / Compostos de Epóxi / Ácidos Graxos / Memória Imunológica / Mitocôndrias Limite: Animals / Child / Child, preschool / Female / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article