FTY720 impairs CD8 T-cell function independently of the sphingosine-1-phosphate pathway
@article{Ntranos2014FTY720IC, title={FTY720 impairs CD8 T-cell function independently of the sphingosine-1-phosphate pathway}, author={Achilles Ntranos and Olivia J Hall and Dionne P. Robinson and Inna V. Grishkan and Jason T. Schott and Dominique M Tosi and Sabra L. Klein and Peter A. Calabresi and Anne R. Gocke}, journal={Journal of Neuroimmunology}, year={2014}, volume={270}, pages={13-21} }
41 Citations
Identification of a novel mechanism of action of fingolimod (FTY720) on human effector T cell function through TCF-1 upregulation
- Biology, MedicineJournal of Neuroinflammation
- 2015
The results reveal a previously unknown mechanism of the effect of FTY720 on human CD4+ T cell modulation in multiple sclerosis and demonstrate the role of TCF-1 in human T cell activation and effector function.
S1P/S1PR1 signaling differentially regulates the allogeneic response of CD4 and CD8 T cells by modulating mitochondrial fission
- Biology, MedicineCellular & Molecular Immunology
- 2022
It is demonstrated that recipient sphingosine kinase 1 (Sphk1), but not Sphk2, was required for optimal S1PR1-dependent donor T-cell allogeneic responses by secreting S1P, which validates Sphk1 or S1 PR1 as a therapeutic target for the prevention of GVHD and leukemia relapse.
Characterization of the effects of immunomodulatory drug fingolimod (FTY720) on human T cell receptor signaling pathways
- Biology, MedicineScientific Reports
- 2018
Data suggest that FTY720 mediated inhibition of TCA is due to inhibition of distal TCR signaling, which may aid in developing novel FTY 720-based immunomodulatory agents.
Fingolimod retains cytolytic T cells and limits T follicular helper cell infection in lymphoid sites of SIV persistence
- Biology, MedicinePLoS pathogens
- 2019
The FTY720-induced inhibition of T cell egress from LN resulted in a measurable decrease of SIV-DNA content in blood as well as in LN Tfh cells in most treated animals, providing rationale for strategies to retain antiviral T cells in lymphoid tissues to target HIV remission.
Fingolimod targeting protein phosphatase 2A differently affects IL‐33 induced IL‐2 and IFN‐γ production in CD8+ lymphocytes
- Biology, MedicineEuropean journal of immunology
- 2016
These findings directly improve the understanding of FTY720 therapy in MS and could also contribute to side effects of F TY720 treatment, like progressive multifocal leukoencephalopathy, caused by an insufficient immune response to a viral infection.
Fingolimod modulates T cell phenotype and regulatory T cell plasticity in vivo.
- Biology, MedicineJournal of autoimmunity
- 2019
Fingolimod therapy modulates circulating B cell composition, increases B regulatory subsets and production of IL-10 and TGFβ in patients with Multiple Sclerosis.
- Biology, MedicineJournal of autoimmunity
- 2016
Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod
- Biology, MedicineInternational journal of molecular sciences
- 2015
The dynamics of systemic and intrathecal immune responses associated with symptomatic VZV reactivation including cessation of fingolimod and initiation of antiviral therapy are studied.
Peripheral myeloid-derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosis
- Biology, PsychologybioRxiv
- 2022
Fingolimod-treated animals presented a milder EAE course with less demyelination and axonal damage, although a few animals did not respond well to treatment and they invariably had fewer M-MDSCs prior to initiating the treatment.
Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential
- BiologyMediators of inflammation
- 2016
Previous findings and new discoveries about the importance of S1P and S1PR signaling in the recruitment of immune cells and lymphocyte retention in inflamed tissues are summarized.
References
SHOWING 1-10 OF 41 REFERENCES
FTY720, sphingosine 1-phosphate receptor modulator, ameliorates experimental autoimmune encephalomyelitis by inhibition of T cell infiltration.
- Biology, MedicineCellular & molecular immunology
- 2005
Results indicate that FTY 720 exhibits not only a prophylactic but also a therapeutic effect on EAE in rats and mice, and that the effect of FTY720 appears to be due to a reduction of the infiltration of myelin antigen-specific CD4(+) T cells into the inflammation site.
Sphingosine Kinase 2 Is Required for Modulation of Lymphocyte Traffic by FTY720*
- Biology, ChemistryJournal of Biological Chemistry
- 2005
Although FTY720 was selectively activated in vivo by SPHK2, other S1P pro-drugs can be phosphorylated to cause lymphopenia through the action of additional sphingosine kinases.
Fingolimod (FTY720), sphingosine 1-phosphate receptor modulator, shows superior efficacy as compared with interferon-β in mouse experimental autoimmune encephalomyelitis.
- Biology, ChemistryInternational immunopharmacology
- 2011
Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720.
- BiologyBlood
- 2006
The generation of sphingosine kinase 2 (SPHK2) knockout mice is reported on and it is demonstrated that this enzyme is essential for FTY720 phosphate formation in vivo, indicating that SPHK2 is constantly required to maintain FTY 720 phosphate levels in vivo.
The immunosuppressant drug FTY720 inhibits cytosolic phospholipase A2 independently of sphingosine-1-phosphate receptors.
- Biology, ChemistryBlood
- 2007
FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system
- BiologyBritish journal of pharmacology
- 2009
FTY720 may act through immune‐based and central mechanisms to reduce inflammation and support structural restoration of the central nervous system parenchyma and short‐term, low‐dose administration of FTY720 could help treat chronic (viral) infections.
Myelin Antigen-Specific CD8+ T Cells Are Encephalitogenic and Produce Severe Disease in C57BL/6 Mice1
- Biology, MedicineThe Journal of Immunology
- 2001
It is reported that synthetic peptides 35–55 from myelin oligodendrocyte glycoprotein (pMOG35–55) consistently activate a high proportion of CD8+ αβTCR+ T cells that are encephalitogenic in C57BL/6 (B6) mice.
Pathogenic CD8 T Cells in Multiple Sclerosis and Its Experimental Models
- Biology, MedicineFront. Immun.
- 2012
Understanding how CNS-reactive CD8 T cells escape tolerance induction and induce CNS autoimmunity is critical to the ability to propose and test new therapies for MS.
Sphingosine 1-phosphate receptor agonists attenuate relapsing–remitting experimental autoimmune encephalitis in SJL mice
- Biology, MedicineJournal of Neuroimmunology
- 2004
Kv1.3 Deletion Biases T Cells toward an Immunoregulatory Phenotype and Renders Mice Resistant to Autoimmune Encephalomyelitis
- BiologyThe Journal of Immunology
- 2012
Skewing of CD4+ T cell differentiation toward Ag-specific regulatory T cells by pharmacological blockade or genetic suppression of Kv1.3 might be beneficial for therapy of immune-mediated diseases such as multiple sclerosis.