ArticleJournal of neuroinflammation2017
Fingolimod additionally acts as immunomodulator focused on the innate immune system beyond its prominent effects on lymphocyte recirculation.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Effects of High Efficacy Multiple Sclerosis Disease Modifying Drugs on the Immune Synapse: A Systematic Review.Current pharmaceutical design · 2024Pooled it
- Effects of fingolimod, a sphingosine-1-phosphate (S1P) receptor agonist, on white matter microstructure, cognition and symptoms in schizophrenia.Brain imaging and behavior · 2021Trial
- Safety and in vivo immune assessment of escalating doses of oral laquinimod in patients with RRMS.Journal of neuroinflammation · 2017Trial
- Cytokine Gene Expression and Treatment Impact on MRI Outcomes in Jordanian Patients with Multiple Sclerosis.Life (Basel, Switzerland) · 2025Article
- How do sphingosine-1-phosphate affect immune cells to resolve inflammation?Frontiers in immunology · 2024Review
- T cell responses to SARS-CoV-2 vaccination differ by disease-modifying therapy for multiple sclerosis.JCI insight · 2023Article
- Influence of exercise on quantity and deformability of immune cells in multiple sclerosis.Frontiers in neurology · 2023Article
- Protein Phosphatase 2A: Role in T Cells and Diseases.Journal of immunology research · 2023Review
- Serum CXCL5 as a biomarker in multiple sclerosis and neuromyelitis optica spectrum disorder.Northern clinics of Istanbul · 2023Article
- Impact of disease-modifying therapy on dendritic cells and exploring their immunotherapeutic potential in multiple sclerosis.Journal of neuroinflammation · 2022Review
- Multiple Sclerosis Management During the COVID-19 Pandemic.Current neurology and neuroscience reports · 2022Review
- Th17 cells in the liver: balancing autoimmunity and pathogen defense.Seminars in immunopathology · 2022Review
- Neuroprotective Potential of Dendritic Cells and Sirtuins in Multiple Sclerosis.International journal of molecular sciences · 2022Review
- Fingolimod treatment modulates PPARγ and CD36 gene expression in women with multiple sclerosis.Frontiers in molecular neuroscience · 2022Article
- S1P receptor modulators and the cardiovascular autonomic nervous system in multiple sclerosis: a narrative review.Therapeutic advances in neurological disorders · 2022Review
- Fingolimod Nanoemulsions at Different Particle Sizes Define the Fate of Spinal Cord Injury Recovery.BioMed research international · 2022Article
- Review
- Transcriptomic Analysis of Peripheral Monocytes upon Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis Patients.Molecular neurobiology · 2021Article
- The effect of fingolimod on regulatory T cells in a mouse model of brain ischaemia.Journal of neuroinflammation · 2021Article
- The Effect of Lipid Metabolism on CD4Mediators of inflammation · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGrowing evidence emphasizes the relevance of sphingolipids for metabolism and immunity of antigen-presenting cells (APC). APCs are key players in balancing tolerogenic and encephalitogenic responses in immunology. In contrast to the well-known prominent effects of sphingosine-1-phosphate (S1P) on lymphocyte trafficking, modulatory effects on APCs have not been fully characterized.
methodsFrequencies and activation profiles of dendritic cell (DC) subtypes, monocytes, and T cell subsets in 35 multiple sclerosis (MS) patients were evaluated prior and after undergoing fingolimod treatment for up to 24 months. Impact of fingolimod and S1P on maturation and activation profile, pro-inflammatory cytokine release, and phagocytotic capacity was assessed in vitro and ex vivo. Modulation of DC-dependent programming of naïve CD4+ T cells, as well as CD4+ and CD8+ T cell proliferation, was also investigated in vitro and ex vivo.
resultsFingolimod increased peripheral slanDC count-CD1+ DC, and monocyte frequencies remained stable. While CD4+ T cell count decreased, ratio of Treg/Th17 significantly increased in fingolimod-treated patients over time. CD83, CD150, and HLADR were all inhibited, but CD86 was upregulated in DCs after incubation in the presence of fingolimod. Fingolimod but not S1P was associated with reduced release of pro-inflammatory cytokines from DCs and monocytes in vitro and ex vivo. Fingolimod also inhibited phagocytic capacity of slanDCs and monocytes. After fingolimod, slanDCs demonstrated reduced potential to induce interferon-gamma-expressing Th1 or IL-17-expressing Th17 cells and DC-dependent T cell proliferation in vitro and in fingolimod-treated patients.
conclusionsWe present the first evidence that S1P-directed therapies can act additionally as immunomodulators that decrease the pro-inflammatory capabilities of APCs, which is a crucial element in DC-dependent T cell activation and programming.
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