Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a letter
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Supplemental material
  • Version history
  • Article usage
  • Citations to this article
Advertisement

ResearchIn-Press PreviewImmunology Open Access | 10.1172/jci.insight.137761

Coordination of asparagine uptake and asparagine synthetase expression modulates CD8+ T cell activation

Helen Carrasco Hope,1 Rebecca J. Brownlie,1 Christopher M. Fife,1 Lynette Steele,1 Mihaela Lorger,1 and Robert J. Salmond2

1Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University Hospital, Leeds, United Kingdom

2Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University HospitalFaculty of Medicine and, Leeds, United Kingdom

Find articles by Hope, H. in: JCI | PubMed | Google Scholar |

1Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University Hospital, Leeds, United Kingdom

2Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University HospitalFaculty of Medicine and, Leeds, United Kingdom

Find articles by Brownlie, R. in: JCI | PubMed | Google Scholar |

1Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University Hospital, Leeds, United Kingdom

2Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University HospitalFaculty of Medicine and, Leeds, United Kingdom

Find articles by Fife, C. in: JCI | PubMed | Google Scholar

1Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University Hospital, Leeds, United Kingdom

2Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University HospitalFaculty of Medicine and, Leeds, United Kingdom

Find articles by Steele, L. in: JCI | PubMed | Google Scholar

1Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University Hospital, Leeds, United Kingdom

2Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University HospitalFaculty of Medicine and, Leeds, United Kingdom

Find articles by Lorger, M. in: JCI | PubMed | Google Scholar |

1Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University Hospital, Leeds, United Kingdom

2Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University HospitalFaculty of Medicine and, Leeds, United Kingdom

Find articles by Salmond, R. in: JCI | PubMed | Google Scholar |

Published April 6, 2021 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.137761.
Copyright © 2021, Hope et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 6, 2021 - Version history
View PDF
Abstract

T cell receptor (TCR) triggering by antigen results in metabolic reprogramming that, in turn, facilitates T cells’ exit from quiescence. The increased nutrient requirements of activated lymphocytes are met in part by upregulation of cell surface transporters and enhanced uptake of amino acids, fatty acids and glucose from the environment. However, the role of intracellular pathways of amino acid biosynthesis in T cell activation is relatively unexplored. Asparagine (Asn) is a non-essential amino acid that can be synthesized intracellularly through the glutamine-hydrolyzing enzyme asparagine synthetase (ASNS). We set out to define the requirements for uptake of extracellular Asn and ASNS activity in CD8+ T cell activation. At early timepoints of activation in vitro, CD8+ T cells expressed little or no ASNS and, as a consequence, viability and TCR-stimulated growth, activation and metabolic reprogramming were substantially impaired under conditions of Asn deprivation. At later timepoints (>24h of activation), TCR-induced mTOR-dependent signals resulted in upregulation of ASNS, that endowed CD8+ T cells with the capacity to function independently of extracellular Asn. Thus, our data suggest that the coordinated upregulation of ASNS expression and uptake of extracellular Asn is involved in optimal T cell effector responses.

Supplemental material

View Supplemental Figures 1-5

Version history
  • Version 1 (April 6, 2021): In-Press Preview

Article tools

  • View PDF
  • Download citation information
  • Send a letter
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Supplemental material
  • Version history
Advertisement
Advertisement

Copyright © 2021 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts