The Translational Machinery of Human CD4 T Cells Is Poised for Activation and Controls the Switch from Quiescence to Metabolic Remodeling.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Crosti, Maria Cristina
MetadataShow full item record
AbstractNaive T cells respond to T cell receptor (TCR) activation by leaving quiescence, remodeling metabolism, initiating expansion, and differentiating toward effector T cells. The molecular mechanisms coordinating the naive to effector transition are central to the functioning of the immune system, but remain elusive. Here, we discover that T cells fulfill this transitional process through translational control. Naive cells accumulate untranslated mRNAs encoding for glycolysis and fatty acid synthesis factors and possess a translational machinery poised for immediate protein synthesis. Upon TCR engagement, activation of the translational machinery leads to synthesis of GLUT1 protein to drive glucose entry. Subsequently, translation of ACC1 mRNA completes metabolic reprogramming toward an effector phenotype. Notably, inhibition of the eIF4F complex abrogates lymphocyte metabolic activation and differentiation, suggesting ACC1 to be a key regulatory node. Thus, our results demonstrate that translation is a direct mediator of T cell metabolism and indicate translation factors as targets for novel immunotherapeutic approaches.
CitationCell Metab. 2018 Dec 4;28(6):895-906.e5. doi: 10.1016/j.cmet.2018.08.009. Epub 2018 Sep 6.
AffiliationHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
PublisherElsevier/ Cell Press
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- High levels of eukaryotic Initiation Factor 6 (eIF6) are required for immune system homeostasis and for steering the glycolytic flux of TCR-stimulated CD4<sup>+</sup> T cells in both mice and humans.
- Authors: Manfrini N, Ricciardi S, Miluzio A, Fedeli M, Scagliola A, Gallo S, Brina D, Adler T, Busch DH, Gailus-Durner V, Fuchs H, Hrabě de Angelis M, Biffo S
- Issue date: 2017 Dec
- Cell surface Glut1 levels distinguish human CD4 and CD8 T lymphocyte subsets with distinct effector functions.
- Authors: Cretenet G, Clerc I, Matias M, Loisel S, Craveiro M, Oburoglu L, Kinet S, Mongellaz C, Dardalhon V, Taylor N
- Issue date: 2016 Apr 12
- Differential Reliance on Lipid Metabolism as a Salvage Pathway Underlies Functional Differences of T Cell Subsets in Poor Nutrient Environments.
- Authors: Ecker C, Guo L, Voicu S, Gil-de-Gómez L, Medvec A, Cortina L, Pajda J, Andolina M, Torres-Castillo M, Donato JL, Mansour S, Zynda ER, Lin PY, Varela-Rohena A, Blair IA, Riley JL
- Issue date: 2018 Apr 17
- In human alloreactive CD4⁺ T-cells, dichloroacetate inhibits aerobic glycolysis, induces apoptosis and favors differentiation towards the regulatory T-cell subset instead of effector T-cell subsets.
- Authors: Eleftheriadis T, Sounidaki M, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I
- Issue date: 2016 Apr
- Akt and STAT5 mediate naïve human CD4+ T-cell early metabolic response to TCR stimulation.
- Authors: Jones N, Vincent EE, Cronin JG, Panetti S, Chambers M, Holm SR, Owens SE, Francis NJ, Finlay DK, Thornton CA
- Issue date: 2019 May 3