Fingolimod modulates peripheral effector and regulatory T cells in MS patients

Laura D. Serpero, Gilberto Filaci, Alessia Parodi, Florinda Battaglia, Francesca Kalli, Davide Brogi, Giovanni Luigi Mancardi, Antonio Uccelli, Daniela Fenoglio

Research output: Contribution to journalArticle

Abstract

Multiple sclerosis (MS) is a complex neurological disease where, in genetically predisposed individuals, the unbalanced interplay between pathogenic and regulatory T cells will result in the progression of the autoimmune assault to neural antigens. Fingolimod (FTY720), an oral sphingosine 1-phosphate modulator recently approved for the treatment of MS, inhibits the egress of T cells from lymph nodes acting specifically on naïve and memory T cells and sparing effector T cells. Here we characterized IL-17 and IFNγ producing effector CD4 and CD8 positive T cells as well as CD4 positive CD25 highCD127low regulatory T cells in MS patients before and 1 month after treatment was started. We observed that fingolimod did not significantly affect the percentage of CCR6 and CD161 positive T cells in both CD4 and CD8 compartments. In contrast, it significantly reduced the levels of both CD4+ CCR6+ CD161+ and CD8+ CCR6+ CD161+ producing IFNγ alone or in combination with IL-17. The percentage of IL-17 secreting cells in both subsets was affected by the treatment to a lesser extent. Finally, we observed that CD4+ CD25highCD127low regulatory T cells were decreased in MS patients compared to healthy controls and fingolimod significantly increased their frequencies. All together these findings demonstrate that fingolimod functionally modulates the ability of potentially pathogenic effector cells to produce relevant pro-inflammatory cytokines and increases the number of circulating regulatory T cells possibly contributing in restoring a balance between these populations.

Original languageEnglish
Pages (from-to)1106-1113
Number of pages8
JournalJournal of NeuroImmune Pharmacology
Volume8
Issue number5
DOIs
Publication statusPublished - Dec 2013

Keywords

  • Fingolimod
  • IFNγ
  • IL-17
  • Multiple sclerosis
  • S1P
  • T cells

ASJC Scopus subject areas

  • Pharmacology
  • Immunology and Allergy
  • Immunology
  • Neuroscience (miscellaneous)

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  • Cite this

    Serpero, L. D., Filaci, G., Parodi, A., Battaglia, F., Kalli, F., Brogi, D., Mancardi, G. L., Uccelli, A., & Fenoglio, D. (2013). Fingolimod modulates peripheral effector and regulatory T cells in MS patients. Journal of NeuroImmune Pharmacology, 8(5), 1106-1113. https://doi.org/10.1007/s11481-013-9465-5