ArticleThe Journal of biological chemistry2013
A disintegrin and metalloprotease (ADAM) 10 and ADAM17 are major sheddases of T cell immunoglobulin and mucin domain 3 (Tim-3).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 138 citations in OpenAlex.
- Soluble Immune Checkpoints and Anti-HLA Antibodies in Kidney Transplant Recipients: Associations With Kidney Function.Immunology · 2026Article
- Unlocking the roles of plasma soluble T-cell immunoglobulin and mucin domain-containing protein 3 in kidney diseases: findings from native and allograft biopsy cohorts.Molecular biomedicine · 2026Article
- The ADAM Family of Proteases: Structure, Substrates, and Roles in Liver Diseases.International journal of molecular sciences · 2026Review
- Immune checkpoint TIM-3 in tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- TIM-3+ Macrophages: Insights into Their Role in Cancer and Inflammation.International journal of molecular sciences · 2026Review
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- The TIM-3/Gal-9 Pathway: A Promising Therapeutic Target for Regulation of Immune Checkpoint in Rheumatoid Arthritis.Current rheumatology reviews · 2026Review
- Soluble TIM-3 and galectin-9 predict survival in gastric and gastroesophageal junction cancer.iScience · 2025Article
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- The Susceptibility Profiles of Human Peripheral Blood Cells toMicroorganisms · 2025Review
- Serum soluble Tim‑3 is elevated in patients with cervical cancer and is higher in advanced clinical stages.Biomedical reports · 2025Article
- Reprogramming the breast tumor immune microenvironment: cold-to-hot transition for enhanced immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Plasma exchange and radiation resensitize immunotherapy-refractory melanoma: a phase I trial.Nature communications · 2025Article
- Soluble TIM-3, likely produced by myeloid cells, predicts resistance to immune checkpoint inhibitors in metastatic clear cell renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Disseminated Kaposi sarcoma patients exhibit an expanded population of CD8+CD57+ T cells and an immunosenescence profile.Frontiers in immunology · 2025Article
- Soluble checkpoint molecules as predictive biomarker for disease activity and long-term outcome in SLE.Frontiers in immunology · 2025Article
- Based on Soluble Immune Checkpoints Constructing a Random Survival Forest Model to Predict the Prognosis of Hepatitis B Virus-Associated Hepatocellular Carcinoma.OncoTargets and therapy · 2025Article
- TIM3 in COVID-19; A potential hallmark?Heliyon · 2024Review
- Unraveling the Intricacies of OPG/RANKL/RANK Biology and Its Implications in Neurological Disorders-A Comprehensive Literature Review.Molecular neurobiology · 2024Review
- Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cell immunoglobulin and mucin domain 3 (Tim-3) dampens the response of CD4(+) and CD8(+) effector T cells via induction of cell death and/or T cell exhaustion and enhances the ability of macrophages to clear pathogens via binding to galectin 9. Here we provide evidence that human Tim-3 is a target of A disintegrin and metalloprotease (ADAM)-mediated ectodomain shedding resulting in a soluble form of Tim-3. We identified ADAM10 and ADAM17 as major sheddases of Tim-3 as shown by ADAM-specific inhibitors and the ADAM10 pro-domain in HEK293 cells and ADAM10/ADAM17-deficient murine embryonic fibroblasts. PMA-induced shedding of Tim-3 was abrogated by deletion of amino acids Glu(181)-Asp(190) of the stalk region and Tim-3 lacking the intracellular domain was not efficiently cleaved after PMA stimulation. Surprisingly, a single lysine residue within the intracellular domain rescues shedding of Tim-3. Shedding of endogenous Tim-3 was found in primary human CD14(+) monocytes after PMA and ionomycin stimulation. Importantly, the recently described down-regulation of Tim-3 from Toll-like receptor-activated CD14(+) monocytes was caused by ADAM10- and ADAM17-mediated shedding. Inhibition of Tim-3 shedding from lipopolysaccharide-induced monocytes did not influence lipopolysaccharide-induced TNFα and IL-6 but increases IL-12 expression. In summary, we describe Tim-3 as novel target for ADAM-mediated ectodomain shedding and suggest a role of Tim-3 shedding in TLR-mediated immune responses of CD14(+) monocytes.
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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.