ArticleScientific reports2018
Characterization of the effects of immunomodulatory drug fingolimod (FTY720) on human T cell receptor signaling pathways.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Incidence and Risk of Infection Associated With Fingolimod in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis of 8,448 Patients From 12 Randomized Controlled Trials.Frontiers in immunology · 2021Pooled it
- Evaluating the Effect of Non-cellular Bioactive Glass-Containing Scaffolds on Osteogenesis and Angiogenesis inFrontiers in bioengineering and biotechnology · 2020Pooled it
- Fingolimod increases cellular resistance to HIV-1 infection and limits viral reservoir size in peripheral CD4+ T-cells.PLoS pathogens · 2026Article
- Chronic Diseases and Influenza Vaccines.Vaccines · 2025Review
- Proteogenomics Reveals Microproteins in Activated T Cells.Molecular & cellular proteomics : MCP · 2025Article
- Article
- CD8Frontiers in cellular and infection microbiology · 2025Article
- FTY720 Reduces the Biomass of Biofilms inAntibiotics (Basel, Switzerland) · 2024Article
- Pharmacological Effects of FTY720 and its Derivatives.Current topics in medicinal chemistry · 2024Review
- TSLP in DRG neurons causes the development of neuropathic pain through T cells.Journal of neuroinflammation · 2023Article
- From gene identifications to therapeutic targets for asthma: Focus on great potentials ofChinese medical journal pulmonary and critical care medicine · 2023Review
- Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration.International journal of molecular sciences · 2023Review
- FTY720 in immuno-regenerative and wound healing technologies for muscle, epithelial and bone regeneration.Frontiers in physiology · 2023Review
- Harnessing the power of sphingolipids: Prospects for acute myeloid leukemia.Blood reviews · 2022Review
- Fingolimod-Conjugated Charge-Altering Releasable Transporters Efficiently and Specifically Deliver mRNA to Lymphocytes In Vivo and In Vitro.Biomacromolecules · 2022Article
- Sphingosine-1-Phosphate Levels Are Higher in Male Patients with Non-Classic Fabry Disease.Journal of clinical medicine · 2022Article
- Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod.Frontiers in pharmacology · 2022Review
- Orosomucoid-like protein 3, rhinovirus and asthma.World journal of critical care medicine · 2021Review
- Ssu72 phosphatase directly binds to ZAP-70, thereby providing fine-tuning of TCR signaling and preventing spontaneous inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Regulation of CTLA-4 and PD-L1 Expression in Relapsing-Remitting Multiple Sclerosis Patients after Treatment with Fingolimod, IFNβ-1α, Glatiramer Acetate, and Dimethyl Fumarate Drugs.Journal of personalized medicine · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune responses against gene therapy products limit its therapeutic efficacy and present a safety risk. Identification of agents that blunt immune reactions may aid in developing novel immunomodulatory therapies. Fingolimod (FTY720) is an FDA approved immunomodulatory drug for treating multiple sclerosis that inhibits lymphocyte egress from lymphoid tissues by down regulating sphingosine-1 phosphate receptor (S1PR). Recent studies found that FTY720 inhibits T cell activation (TCA) in a S1PR-independent manner; however, the mechanism is incompletely understood. Here we characterized the effects of FTY720 on human T cell receptor (TCR) signaling pathways. FTY720 inhibited both the TCR-dependent and independent activation of primary human T cells. FTY720 did not affect proximal TCR signaling events as measured by phosphorylation of Lck, ZAP-70 and LAT; however, inhibited PMA/Ionomycin induced distal TCR signaling as measured by IL-2, IFN-γ release and CD25 expression. FTY720 induced aberrant NFAT1, AP1 and NFκB activation which were associated with increased acetylation of histone (H3K9). Phosphorylated FTY720 did not inhibit TCA, and arachidonic acid did not rescue FTY720 mediated inhibition of TCA. These data suggest that FTY720 mediated inhibition of TCA is due to inhibition of distal TCR signaling. Understanding FTY720-mediated inhibition of TCA may aid in developing novel FTY720-based immunomodulatory agents.
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