Article ; Online: Ozanimod-mediated remission in experimental autoimmune encephalomyelitis is associated with enhanced activity of CNS CD27
2024 Volume 15, Page(s) 1230735
Abstract: Background: Ozanimod (RPC1063) is an immunomodulator that has been recently approved by the FDA (2020) for the treatment of relapsing-remitting multiple sclerosis (RRMS). It is a selective agonist of the sphingosine-1-phophate receptors 1 and 5, ... ...
| Abstract | Background: Ozanimod (RPC1063) is an immunomodulator that has been recently approved by the FDA (2020) for the treatment of relapsing-remitting multiple sclerosis (RRMS). It is a selective agonist of the sphingosine-1-phophate receptors 1 and 5, expressed on naïve and central memory T and B cells, as well as natural killer (NK) cells, and is involved in lymphocyte trafficking. Oral administration of ozanimod was reported to result in rapid and reversible reduction in circulating lymphocytes in multiple sclerosis (MS) patients, however, only minimal effect on NK cells was observed. In this study, we sought to investigate the effect of ozanimod on NK cells and assess whether they play any role in ozanimod-induced remission in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Methods: Active EAE induction was done in C57BL/6 female mice, followed by daily oral treatment with ozanimod (0.6mg/kg) starting at disease onset (score 1). Flow cytometry of blood and CNS was performed 24 hours after the last oral dose of ozanimod treatment in diseased mice. Histological analysis of lumbar spinal cord was performed for evaluating the level of inflammation and demyelination. Depletion of peripheral NK cells was done using anti-NK1.1 mouse antibody (mAb) at day 5 post-EAE induction. Results: Ozanimod was effective in reducing the clinical severity of EAE and reducing the percentage of autoreactive CD4 Conclusion: The current study demonstrated that ozanimod treatment significantly improved clinical symptoms in EAE mice. Ozanimod and anti-NK1.1 mAb appear to function in opposition to one another. Collectively, our data suggest that ozanimod-mediated remission is associated with an increased percentage of total NK cells and CD27 |
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| MeSH term(s) | Humans ; Female ; Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental ; CD8-Positive T-Lymphocytes ; Mice, Inbred C57BL ; Multiple Sclerosis ; Killer Cells, Natural ; Indans ; Oxadiazoles |
| Chemical Substances | ozanimod (Z80293URPV) ; Indans ; Oxadiazoles |
| Language | English |
| Publishing date | 2024-03-12 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2606827-8 |
| ISSN | 1664-3224 ; 1664-3224 |
| ISSN (online) | 1664-3224 |
| ISSN | 1664-3224 |
| DOI | 10.3389/fimmu.2024.1230735 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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