What question did this study set out to answer?

To investigate the direct regulatory effects of fingolimod (FTY720) on human CD4+ T cell activation and effector function in multiple sclerosis.

December 1, 2015Journal of NeuroinflammationOpen Access

Identification of a novel mechanism of action of fingolimod (FTY720) on human effector T cell function through TCF-1 upregulation

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Authors

MMMaria Antonietta MazzolaLahey Hospital and Medical Center RRRadhika RahejaShri Vile Parle Kelavani Mandal GMGopal MurugaiyanBrigham and Women's Hospital

Discussion

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Implication

Translational study demonstrates fingolimod dampens inflammatory effector T cell activity in multiple sclerosis, highlighting an immune-regulatory role for TCF-1 beyond lymphocyte trafficking.

Key Points

To investigate the direct regulatory effects of fingolimod (FTY720) on human CD4+ T cell activation and effector function in multiple sclerosis.
Isolated T cells from multiple sclerosis patients and healthy controls to assess gene and cytokine expression with NanoString, RT-qPCR, Luminex assays, and flow cytometry.
Investigated molecular mechanisms in CD4+ T cells using shRNA-mediated knockdown, chromatin immunoprecipitation, luciferase reporter assays, and Western blotting for Akt and GSK3β phosphorylation.
FTY720 treatment significantly reduced circulating CD4+ T cells and fostered a less inflammatory phenotype marked by reduced production of IFN-γ and granzyme B.
FTY720-induced upregulation of TCF-1 mediated the direct transcriptional and epigenetic repression of pathogenic IFN-γ and granzyme B by binding their promoter and enhancer regions.
Baseline TCF-1 expression was lower in T cells from multiple sclerosis patients than in healthy individuals, but was restored and increased following FTY720 therapy.

Cite This Study

Mazzola et al. (2015) studied this question.

synapsesocial.com/papers/6aa90da8022accd6d12c90e4 https://doi.org/10.1186/s12974-015-0460-z

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Implication

Translational study demonstrates fingolimod dampens inflammatory effector T cell activity in multiple sclerosis, highlighting an immune-regulatory role for TCF-1 beyond lymphocyte trafficking.

Identification of a novel mechanism of action of fingolimod (FTY720) on human effector T cell function through TCF-1 upregulation

Discussion

Member takes

Implication

Key Points

Cite This Study

Identification of a novel mechanism of action of fingolimod (FTY720) on human effector T cell function through TCF-1 upregulation

Discussion

Member takes

Implication

Key Points

Cite This Study

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