ArticleThe Journal of biological chemistry2013
CD154 is released from T-cells by a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and ADAM17 in a CD40 protein-dependent manner.
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 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- Soluble CD40 Levels in Rheumatoid Arthritis: Association with Serum Cytokines and Autoantibody Status.Journal of clinical medicine · 2026Article
- Article
- The CD40-CD154 axis in transplantation: from immunobiology to therapeutic targeting.Frontiers in immunology · 2026Review
- Differential response to ofatumumab in anti-AChR and anti-MuSK positive myasthenia gravis patients: a single-center retrospective study.Therapeutic advances in neurological disorders · 2026Article
- Blockade of colon cancer metastasis via single and double silencing ofJournal for immunotherapy of cancer · 2025Article
- The role of soluble CD40L in autoimmune diseases.Journal of translational autoimmunity · 2025Review
- Implications of CD154 and Its Receptors in the Pathogenesis and Treatment of Systemic Lupus Erythematosus.Cells · 2024Review
- Harnessing the potential of CD40 agonism in cancer therapy.Cytokine & growth factor reviews · 2024Review
- CD40 Ligand-CD40 Interaction Is an Intermediary between Inflammation and Angiogenesis in Proliferative Diabetic Retinopathy.International journal of molecular sciences · 2023Article
- B cell peripheral tolerance is promoted by cathepsin B protease.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles.Nature communications · 2022Article
- Novel Functions of Integrins as Receptors of CD154: Their Role in Inflammation and Apoptosis.Cells · 2022Review
- CD40-CD40L in Neurological Disease.International journal of molecular sciences · 2022Review
- Immune Responses to IAV Infection and the Roles of L-Selectin and ADAM17 in Lymphocyte Homing.Pathogens (Basel, Switzerland) · 2022Review
- Immunomodulatory role of metalloproteases in cancers: Current progress and future trends.Frontiers in immunology · 2022Review
- Molecular basis and therapeutic implications of CD40/CD40L immune checkpoint.Pharmacology & therapeutics · 2021Review
- Double Strike Approach for Tumor Attack: Engineering T Cells Using a CD40L:CD28 Chimeric Co-Stimulatory Switch Protein for Enhanced Tumor Targeting in Adoptive Cell Therapy.Frontiers in immunology · 2021Article
- Unique Sjögren's syndrome patient subsets defined by molecular features.Rheumatology (Oxford, England) · 2020Article
- CD40L membrane retention enhances the immunostimulatory effects of CD40 ligation.Scientific reports · 2020Article
- Modulation of Immune Responses by Platelet-Derived ADAM10.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
CD154 (CD40 ligand) is a type II transmembrane protein that belongs to the tumor necrosis factor superfamily. The soluble form of CD154 (sCD154), which results from the shedding of membrane-bound CD154, plays a key role in the production of proinflammatory cytokines and has been linked to various autoimmune and vascular disorders. Therefore, elucidating the mechanisms by which CD154 is released from the cell surface following its interaction with its various receptors is of primordial importance. Using co-culture experiments, we show that CD154 is shed predominantly upon its engagement with CD40. Indeed, only CD40 (both membrane-bound and soluble) and not α5β1 or αMβ2 is involved in the cleavage and release of CD154 from Jurkat E6.1 T-cells. Interestingly, CD154 is cleaved independently of the formation of cell surface CD40 homodimers and independently of its association into lipid rafts. In contrast, we found that the protein kinase C (PKC) signaling family and the matrix metalloproteinases ADAM10 and ADAM17 are intimately involved in this process. In conclusion, our data indicate that CD154 is released from T-cells by ADAM10 and ADAM17 upon CD40 ligation. These findings add significant insights into the mechanisms by which CD154 is down-regulated and may lead to the generation of novel therapeutic targets for the treatment of CD154-associated disorders.
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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.