ArticleJCI insight2021
Coordination of asparagine uptake and asparagine synthetase expression modulates CD8+ T cell activation.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- Comparative analysis of amino acid profiles across pediatric groups stratified by asthma and IgE-dependent allergy showed differences in serum asparagine levels.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Glutamine-dependent biosynthetic pathways fuel autoreactive T and B cells in Foxp3 deficiency-mediated disease.JCI insight · 2026Article
- L-asparaginase reversibly suppresses CD40-mediated B cell activation and antigen-presenting function by metabolic restriction.iScience · 2026Article
- Article
- How crosstalk at the immune synapse shapes T cell and dendritic cell biology.Nature reviews. Immunology · 2026Review
- Metabolic modulation of immune cell function: mechanisms and therapeutic implications in cancer immunotherapy.Oncogenesis · 2026Review
- Tertiary lymphoid structure-related genes drive tumor microenvironment heterogeneity and prognostic disparities in left-Translational cancer research · 2026Article
- Tumor metabolic adaptation induced by L-asparaginase reveals a vulnerability to PARP1/2 inhibitor in B-cell lymphomas.Nature communications · 2026Article
- Integrating T cell signaling and metabolism to enhance T cell engager responses in solid tumors.Frontiers in immunology · 2026Review
- Phospho-enol pyruvate carboxykinase inhibition limits effector function in inflammatory T cells.Frontiers in immunology · 2026Article
- ASNS-dependent asparagine availability supports intestinal ILC2 responses and type 2 immunity under nutrient-limited conditions.Frontiers in immunology · 2026Article
- Beyond Protein Building Blocks: A Review of Biological Roles and Therapeutic Potential of Free Amino Acids.International journal of molecular sciences · 2025Review
- Asparaginase enhances CAR-T cell antitumor immunity by asparagine metabolic reprogramming and central memory induction in ALL.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Ensemble quantitation of absolute metabolite concentrations in T cells reveals conserved features of immunometabolism.bioRxiv : the preprint server for biology · 2025Article
- Asparagine drives immune evasion in bladder cancer via RIG-I stability and type I IFN signaling.The Journal of clinical investigation · 2025Article
- Metabolism of Tryptophan, Glutamine, and Asparagine in Cancer Immunotherapy-Synergism or Mechanism of Resistance?Metabolites · 2025Review
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- Lung Cancer Cell-intrinsic Asparagine Synthetase Potentiates Anti-Tumor Immunity via Modulating Immunogenicity and Facilitating Immune Remodeling in Metastatic Tumor-draining Lymph Nodes.International journal of biological sciences · 2025Article
- Asparagine availability controls germinal center B cell homeostasis.Science immunology · 2024Article
- Metabolic footprint and logic through the T cell life cycle.Current opinion in immunology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
T cell receptor (TCR) triggering by antigen results in metabolic reprogramming that, in turn, facilitates the exit of T cells 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 is a nonessential 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 asparagine and ASNS activity in CD8+ T cell activation. At early time points 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 asparagine deprivation. At later time points (more than 24 hours of activation), TCR-induced mTOR-dependent signals resulted in ASNS upregulation that endowed CD8+ T cells with the capacity to function independently of extracellular asparagine. Thus, our data suggest that the coordinated upregulation of ASNS expression and uptake of extracellular asparagine is involved in optimal T cell effector responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.