Dynamics in protein translation sustaining T cell preparedness.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
19
03
2018
accepted:
19
05
2020
pubmed:
8
7
2020
medline:
5
11
2020
entrez:
8
7
2020
Statut:
ppublish
Résumé
In response to pathogenic threats, naive T cells rapidly transition from a quiescent to an activated state, yet the underlying mechanisms are incompletely understood. Using a pulsed SILAC approach, we investigated the dynamics of mRNA translation kinetics and protein turnover in human naive and activated T cells. Our datasets uncovered that transcription factors maintaining T cell quiescence had constitutively high turnover, which facilitated their depletion following activation. Furthermore, naive T cells maintained a surprisingly large number of idling ribosomes as well as 242 repressed mRNA species and a reservoir of glycolytic enzymes. These components were rapidly engaged following stimulation, promoting an immediate translational and glycolytic switch to ramp up the T cell activation program. Our data elucidate new insights into how T cells maintain a prepared state to mount a rapid immune response, and provide a resource of protein turnover, absolute translation kinetics and protein synthesis rates in T cells ( https://www.immunomics.ch ).
Identifiants
pubmed: 32632289
doi: 10.1038/s41590-020-0714-5
pii: 10.1038/s41590-020-0714-5
pmc: PMC7610365
mid: EMS117975
doi:
Substances chimiques
RNA, Messenger
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
927-937Subventions
Organisme : Swiss National Science Foundation
ID : 170213
Pays : Switzerland
Organisme : European Research Council
ID : 803150
Pays : International
Commentaires et corrections
Type : CommentIn
Références
Crabtree, G. R. Contingent genetic regulatory events in T lymphocyte activation. Science 243, 355–361 (1989).
pubmed: 2783497
Vrisekoop, N. et al. Sparse production but preferential incorporation of recently produced naive T cells in the human peripheral pool. Proc. Natl Acad. Sci. USA 105, 6115–6120 (2008).
pubmed: 18420820
Chapman, N. M., Boothby, M. R. & Chi, H. Metabolic coordination of T cell quiescence and activation. Nat. Rev. Immunol. 20, 55–70 (2020).
pubmed: 31406325
Pearce, E. L., Poffenberger, M. C., Chang, C.-H. & Jones, R. G. Fueling immunity: insights into metabolism and lymphocyte function. Science 342, 1242454 (2013).
pubmed: 24115444
pmcid: 4486656
Fox, C. J., Hammerman, P. S. & Thompson, C. B. Fuel feeds function: energy metabolism and the T-cell response. Nat. Rev. Immunol. 5, 844–852 (2005).
pubmed: 16239903
Araki, K. et al. Translation is actively regulated during the differentiation of CD8
pubmed: 28714979
pmcid: 5937989
Sinclair, L. V. et al. Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nat. Immun. 14, 500–508 (2013).
Gubser, P. M. et al. Rapid effector function of memory CD8
pubmed: 23955661
Buck, M. D., Sowell, R. T., Kaech, S. M. & Pearce, E. L. Metabolic instruction of immunity. Cell 169, 570–586 (2017).
pubmed: 28475890
pmcid: 5648021
Geiger, R. et al. L-Arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell 167, 829–842.e13 (2016).
pubmed: 27745970
pmcid: 5075284
Howden, A. J. et al. Quantitative analysis of T cell proteomes and environmental sensors during T cell differentiation. Nat. Immunol. 20, 1542–1554 (2019).
pubmed: 31591570
pmcid: 6859072
Ron-Harel, N. et al. Mitochondrial biogenesis and proteome remodeling promote one-carbon metabolism for T cell activation. Cell Metab. 24, 104–117 (2016).
pubmed: 27411012
pmcid: 5330619
Kaech, S. M., Hemby, S., Kersh, E. & Ahmed, R. Molecular and functional profiling of memory CD8 T cell differentiation. Cell 111, 837–851 (2002).
pubmed: 12526810
Phan, A. T., Goldrath, A. W. & Glass, C. K. Metabolic and epigenetic coordination of T cell and macrophage immunity. Immunity 46, 714–729 (2017).
pubmed: 28514673
pmcid: 5505665
Schwanhäusser, B. et al. Global quantification of mammalian gene expression control. Nature 473, 337–342 (2011).
pubmed: 21593866
Ong, S.-E. et al. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol. Cell. Proteom. 1, 376–386 (2002).
Jovanovic, M. et al. Dynamic profiling of the protein life cycle in response to pathogens. Science 347, 1259038 (2015).
pubmed: 25745177
pmcid: 4506746
Aebersold, R. & Mann, M. Mass-spectrometric exploration of proteome structure and function. Nature 537, 347–355 (2016).
pubmed: 27629641
Wiśniewski, J. R. et al. Extensive quantitative remodeling of the proteome between normal colon tissue and adenocarcinoma. Mol. Syst. Biol. 8, 611 (2012).
pubmed: 22968445
pmcid: 3472694
Bjørkøy, G. et al. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J. Cell Biol. 171, 603–614 (2005).
pubmed: 16286508
pmcid: 2171557
Wu, N. et al. AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1. Mol. Cell 49, 1167–1175 (2013).
pubmed: 23453806
pmcid: 3615143
Weinreich, M. A. et al. KLF2 transcription-factor deficiency in T cells results in unrestrained cytokine production and upregulation of bystander chemokine receptors. Immunity 31, 122–130 (2009).
pubmed: 19592277
pmcid: 2724594
Muthusamy, N., Barton, K. & Leiden, J. M. Defective activation and survival of T cells lacking the Ets-1 transcription factor. Nature 377, 639–642 (1995).
pubmed: 7566177
Bories, J.-C. et al. Increased T-cell apoptosis and terminal B-cell differentiation induced by inactivation of the Ets-1 proto-oncogene. Nature 377, 635–638 (1995).
pubmed: 7566176
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213–1218 (2013).
pubmed: 24097267
pmcid: 3959825
Froehlich, J. et al. FAM65B controls the proliferation of transformed and primary T cells. Oncotarget 7, 63215 (2016).
pubmed: 27556504
pmcid: 5325358
Binnewies, M. et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 24, 541–550 (2018).
pubmed: 29686425
pmcid: 5998822
Zheng, C. et al. Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell 169, e1316 (2017).
Morisaki, T. et al. Real-time quantification of single RNA translation dynamics in living cells. Science 352, 1425–1429 (2016).
pubmed: 27313040
Wu, B., Eliscovich, C., Yoon, Y. J. & Singer, R. H. Translation dynamics of single mRNAs in live cells and neurons. Science 352, 1430–1435 (2016).
pubmed: 27313041
pmcid: 4939616
Yan, X., Hoek, T. A., Vale, R. D. & Tanenbaum, M. E. Dynamics of translation of single mRNA molecules in vivo. Cell 165, 976–989 (2016).
pubmed: 27153498
pmcid: 4889334
Wang, C., Han, B., Zhou, R. & Zhuang, X. Real-time imaging of translation on single mRNA transcripts in live cells. Cell 165, 990–1001 (2016).
pubmed: 27153499
pmcid: 4905760
Thoreen, C. C. et al. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 485, 109–113 (2012).
pubmed: 22552098
pmcid: 3347774
Thoreen, C. C. et al. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J. Biol. Chem. 284, 8023–8032 (2009).
pubmed: 19150980
pmcid: 2658096
Yang, K., Neale, G., Green, D. R., He, W. & Chi, H. The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function. Nat. Immunol. 12, 888–897 (2011).
pubmed: 21765414
pmcid: 3158818
Iezzi, G., Karjalainen, K. & Lanzavecchia, A. The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity 8, 89–95 (1998).
pubmed: 9462514
Harndahl, M., Rasmussen, M., Roder, G. & Buus, S. Real-time, high-throughput measurements of peptide–MHC-I dissociation using a scintillation proximity assay. J. Immunol. Methods 374, 5–12 (2011).
pubmed: 21044632
Lipford, J. R. & Deshaies, R. J. Diverse roles for ubiquitin-dependent proteolysis in transcriptional activation. Nat. Cell Biol. 5, 845–850 (2003).
pubmed: 14523392
Ingolia, N. T., Lareau, L. F. & Weissman, J. S. Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell 147, 789–802 (2011).
pubmed: 22056041
pmcid: 3225288
Sharova, L. V. et al. Database for mRNA half-life of 19 977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells. DNA Res. 16, 45–58 (2008).
pubmed: 19001483
pmcid: 2644350
Shiow, L. R. et al. CD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature 440, 540–544 (2006).
pubmed: 16525420
Ricciardi, S. et al. The Translational Machinery of Human CD4
pubmed: 30197303
pmcid: 6773601
Tan, T. C. et al. Suboptimal T-cell receptor signaling compromises protein translation, ribosome biogenesis, and proliferation of mouse CD8 T cells. Proc. Natl Acad. Sci. USA 114, E6117–E6126 (2017).
pubmed: 28696283
Liebmann, M. et al. Nur77 serves as a molecular brake of the metabolic switch during T cell activation to restrict autoimmunity. Proc. Natl Acad. Sci. USA 115, E8017–E8026 (2018).
pubmed: 30072431
Kouzine, F. et al. Global regulation of promoter melting in naive lymphocytes. Cell 153, 988–999 (2013).
pubmed: 23706737
pmcid: 3684982
Shapiro, E., Biezuner, T. & Linnarsson, S. Single-cell sequencing-based technologies will revolutionize whole-organism science. Nat. Rev. Genet. 14, 618–630 (2013).
pubmed: 23897237
Akat, K. et al. Molecular characterization of desmosomes in meningiomas and arachnoidal tissue. Acta Neuropathol. 106, 337–347 (2003).
pubmed: 12845453
Hohenberg, H., Mannweiler, K. & Müller, M. High-pressure freezing of cell suspensions in cellulose capillary tubes. J. Microsc. 175, 34–43 (1994).
pubmed: 7932676
Cardona, A. et al. An integrated micro-and macroarchitectural analysis of the Drosophila brain by computer-assisted serial section electron microscopy. PLoS Biol. 8, e1000502 (2010).
pubmed: 20957184
pmcid: 2950124
Kremer, J. R., Mastronarde, D. N. & McIntosh, J. R. Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71–76 (1996).
pubmed: 8742726
Rappsilber, J., Mann, M. & Ishihama, Y. Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nat. Protoc. 2, 1896–1906 (2007).
pubmed: 17703201
Scheltema, R. A. et al. The Q Exactive HF, a benchtop mass spectrometer with a pre-filter, high-performance quadrupole and an ultra-high-field Orbitrap analyzer. Mol. Cell. Proteom. 13, 3698–3708 (2014).
Cox, J. & Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367–1372 (2008).
Cox, J. et al. Andromeda: a peptide search engine integrated into the MaxQuant environment. J. Proteome Res. 10, 1794–1805 (2011).
pubmed: 21254760
pmcid: 21254760
Blecher-Gonen, R. et al. High-throughput chromatin immunoprecipitation for genome-wide mapping of in vivo protein–DNA interactions and epigenomic states. Nat. Protoc. 8, 539–554 (2013).
pubmed: 23429716
Barozzi, I., Termanini, A., Minucci, S. & Natoli, G. Fish the ChIPs: a pipeline for automated genomic annotation of ChIP-Seq data. Biol. Direct 6, 51 (2011).
pubmed: 21978789
pmcid: 3201895
Machanick, P. & Bailey, T. L. MEME-ChIP: motif analysis of large DNA datasets. Bioinformatics 27, 1696–1697 (2011).
pubmed: 21486936
pmcid: 21486936
McLean, C. Y. et al. GREAT improves functional interpretation of cis-regulatory regions. Nat. Biotechnol. 28, 495–501 (2010).
pubmed: 20436461
pmcid: 4840234
Wiśniewski, J. R., Hein, M. Y., Cox, J. & Mann, M. A “proteomic ruler” for protein copy number and concentration estimation without spike-in standards. Mol. Cell. Proteom. 13, 3497–3506 (2014).