Transcriptional effects of fingolimod treatment on peripheral T cells in relapsing remitting multiple sclerosis patients

Pharmacogenomics. 2022 Feb;23(3):161-171. doi: 10.2217/pgs-2021-0118. Epub 2022 Jan 24.

Abstract

Aim: To investigate the transcriptional changes induced by Fingolimod (FTY) in T cells of relapsing remitting multiple sclerosis patients. Patients & methods: Transcriptomic changes after 6 months of FTY therapy were evaluated on T cells from 24 relapsing remitting multiple sclerosis patients through RNA-sequencing, followed by technical validation and pathway analysis. Results: Among differentially expressed genes, CX3CR1 and CCR7 resulted strongly up- and downregulated, respectively. Two relevant genes were validated with quantitative PCR and we largely confirmed findings from two previous microarray-based studies with similar design. Pathway analysis pointed to an involvement of processes related to immune function and cell migration. Conclusion: Our data support the evidence that FTY induces major transcriptional changes in genes involved in immune response and cell trafficking in T lymphocytes.

Keywords: Fingolimod; T lymphocytes; multiple sclerosis; pathway analysis; transcriptomic profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CX3C Chemokine Receptor 1 / metabolism
  • Female
  • Fingolimod Hydrochloride / therapeutic use*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Oligonucleotide Array Sequence Analysis
  • Receptors, CCR7 / metabolism
  • Sequence Analysis, RNA
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transcriptome / drug effects*

Substances

  • CCR7 protein, human
  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human
  • Immunosuppressive Agents
  • Receptors, CCR7
  • Fingolimod Hydrochloride