ArticleScience signaling2021
The costimulatory activity of Tim-3 requires Akt and MAPK signaling and its recruitment to the immune synapse.
Article in Science signaling, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- The multifaceted landscape of T cell exhaustion in organ transplantation: From molecular mechanisms (epigenetics, transcription, metabolism) to induction strategies.Genes & diseases · 2026Review
- Soluble Uric Acid Drives CD8+ T-cell Exhaustion by Inducing KSR1-Mediated MAPK Hyperactivation.Cancer research · 2026Article
- TIM-3, a potential target for sepsis therapy.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2026Review
- Mannose-binding lectin 2 secreted by hepatocellular carcinoma cells recruits and activates natural killer cells to reshape an immune-activated microenvironment.PLoS biology · 2026Article
- TIM-3 in Cardiovascular Disease.Current heart failure reports · 2026Review
- Tim-3 agonist restrains ILC2 function and attenuates airway hyperreactivity via NLK pathway.Nature communications · 2026Article
- The role of the TIM-3 receptor in inflammatory bowel disease and autoimmunity: implications for TIM-3 and TCR crosstalk.Journal of molecular medicine (Berlin, Germany) · 2026Review
- High-throughput discovery of transmembrane helix dimers from human single-pass membrane proteins with TOXGREEN sort-seq.PNAS nexus · 2025Article
- CD226 identifies effector CD8Cell reports · 2025Article
- Article
- Exploring new frontiers in LAG-3 biology and therapeutics.Trends in pharmacological sciences · 2025Review
- Tumour interstitial fluid-enriched phosphoethanolamine suppresses T cell function.Nature cell biology · 2025Article
- Tim-3 pathway dysregulation and targeting in sepsis-induced immunosuppression.European journal of medical research · 2024Review
- Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.Signal transduction and targeted therapy · 2024Review
- Review
- Tim-3 Is Not Required for Establishment of CD8+ T Cell Memory to Lymphocytic Choriomeningitis Virus.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Rewiring the T cell-suppressive cytokine landscape of the tumor microenvironment: a new frontier for precision anti-cancer therapy.Frontiers in immunology · 2024Review
- Myeloid-Derived Suppressor Cells Induce Exhaustion-Like CD8International journal of biological sciences · 2024Article
- Role of TIM-3 in ovarian cancer: the forsaken cop or a new noble.Frontiers in immunology · 2024Review
- Ligand-based, piggyBac-engineered CAR-T cells targeting EGFR are safe and effective against non-small cell lung cancers.Molecular therapy oncolytics · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Expression of the transmembrane protein Tim-3 is increased on dysregulated T cells undergoing chronic activation, including during chronic infection and in solid tumors. Thus, Tim-3 is generally thought of as an inhibitory protein. We and others previously reported that under some circumstances, Tim-3 exerts paradoxical costimulatory activity in T cells (and other cells), including enhancement of the phosphorylation of ribosomal S6 protein. Here, we examined the upstream signaling pathways that control Tim-3-mediated increases in phosphorylated S6 in T cells. We also defined the localization of Tim-3 relative to the T cell immune synapse and its effects on downstream signaling. Recruitment of Tim-3 to the immune synapse was mediated exclusively by the transmembrane domain, replacement of which impaired the ability of Tim-3 to costimulate T cell receptor (TCR)-dependent S6 phosphorylation. Furthermore, enforced localization of the Tim-3 cytoplasmic domain to the immune synapse in a chimeric antigen receptor still enabled T cell activation. Together, our findings are consistent with a model whereby Tim-3 enhances TCR-proximal signaling under acute conditions.
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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.