Fingolimod modulates T cell phenotype and regulatory T cell plasticity in vivo

J Autoimmun. 2019 Jan:96:40-49. doi: 10.1016/j.jaut.2018.08.002. Epub 2018 Aug 16.

Abstract

Fingolimod is an approved therapeutic option for patients with relapsing-remitting multiple sclerosis that primarily functions by sequestering T cells in lymph nodes inhibiting their egress to the central nervous system. However, recent data suggests that Fingolimod may also directly affect the immune cell function. Here we examined the in vivo effects of Fingolimod in modulating the phenotype and function of T cell and Foxp3 regulatory T cell populations in patients with multiple sclerosis under Fingolimod treatment. Besides decreasing the cell numbers in peripheral blood and sera levels of pro-inflammatory cytokines, Fingolimod inhibited the expression of Th1 and Th17 cytokines on CD4+ T cells and increased the expression of exhaustion markers. Furthermore, treatment increased the frequency of regulatory T cells in blood and inhibited the Th1-like phenotype that is characteristic of patients with multiple sclerosis, augmenting the expression of markers associated with increased suppressive function. Overall, our data suggest that Fingolimod performs other important immunomodulatory functions besides altering T cell migratory capacities, with consequences for other autoimmune pathologies characterized by excessive Th1/Th17 responses and Th1-like regulatory T cell effector phenotypes.

Keywords: Fingolimod; Foxp3; Gilenya; Multiple sclerosis; Regulatory T cells; Th1-like Tregs; Treg plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Plasticity
  • Female
  • Fingolimod Hydrochloride / therapeutic use*
  • Humans
  • Immunologic Factors / therapeutic use*
  • Immunophenotyping
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*
  • Young Adult

Substances

  • Immunologic Factors
  • Fingolimod Hydrochloride