ArticleScience immunology2021
Activation of mTORC1 at late endosomes misdirects T cell fate decision in older individuals.
Article in Science immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 41 citations in OpenAlex.
- Metabolic exhaustion and immune ageing in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- [Autoimmunity and ageing : How immune ageing shapes disease phenotype, infection risk and treatment safety in rheumatic diseases].Zeitschrift fur Rheumatologie · 2026Review
- Immune responses in aging adults.The Journal of clinical investigation · 2026Review
- mTOR inhibition augments antitumor immune effector response by reprogramming thebioRxiv : the preprint server for biology · 2026Article
- BLOC1S1 regulates autolysosomal and exosomal dynamics during CD4bioRxiv : the preprint server for biology · 2026Article
- Direct targeting of C9ORF72 repeat RNA with fluorinated antisense oligonucleotides.Nucleic acids research · 2026Article
- Single-cell profiling reveals immunometabolic remodeling with T-cell dysfunction in HIV-1 infected people.Infectious diseases & immunity · 2026Article
- Targeting organelle function in T cells for cancer immunotherapy.Nature reviews. Immunology · 2026Review
- Immune cells harbor their own microbiome-derived metabolome: a new layer of immunometabolic regulation.Frontiers in immunology · 2026Review
- SLC7A5 serves as a potential therapeutic target for osteosarcoma: a comprehensive analysis based on bioinformatics and experimental validation.American journal of cancer research · 2026Article
- Slc7a5 promotes T cell anti-tumor immunity through sustaining cytotoxic T lymphocyte effector function.Oncogene · 2025Article
- Understanding and improving vaccine efficacy in older adults.Nature aging · 2025Review
- Immune Aging in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Review
- Sustained mTORC1 activation in activated T cells impairs vaccine responses in older individuals.Science advances · 2025Article
- Metabolic Signaling as a Driver of T Cell Aging.Immune network · 2025Review
- Review
- Diet switch pre-vaccination improves immune response and metabolic status in formerly obese mice.Nature microbiology · 2024Article
- CD4Cells · 2024Review
- Glutaminolysis of CD4Journal of inflammation research · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The nutrient-sensing mammalian target of rapamycin (mTOR) is integral to cell fate decisions after T cell activation. Sustained mTORC1 activity favors the generation of terminally differentiated effector T cells instead of follicular helper and memory T cells. This is particularly pertinent for T cell responses of older adults who have sustained mTORC1 activation despite dysfunctional lysosomes. Here, we show that lysosome-deficient T cells rely on late endosomes rather than lysosomes as an mTORC1 activation platform, where mTORC1 is activated by sensing cytosolic amino acids. T cells from older adults have an increased expression of the plasma membrane leucine transporter SLC7A5 to provide a cytosolic amino acid source. Hence, SLC7A5 and VPS39 deficiency (a member of the HOPS complex promoting early to late endosome conversion) substantially reduced mTORC1 activities in T cells from older but not young individuals. Late endosomal mTORC1 is independent of the negative-feedback loop involving mTORC1-induced inactivation of the transcription factor TFEB that controls expression of lysosomal genes. The resulting sustained mTORC1 activation impaired lysosome function and prevented lysosomal degradation of PD-1 in CD4
Indexed as
Identifiers
What OpenQuestion holds
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.