High-Resolution Expression Profiling of Peripheral Blood CD8 + Cells in Patients with Multiple Sclerosis Displays Fingolimod-Induced Immune Cell Redistribution

摘要: Fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator, is an oral drug approved for the treatment of active relapsing-remitting multiple sclerosis (RRMS). It selectively inhibits egress lymphocytes from lymph nodes. We studied changes in transcriptome peripheral blood CD8+ cells to unravel effects at molecular level during fingolimod therapy. separated RRMS patients before first dose as well 24 h and 3 months after start Changes expression coding non-coding genes were measured with high-density Affymetrix Human Transcriptome Array (HTA) 2.0 microarrays. Differentially expressed response therapy identified by t test fold change analyzed their functions interactions. No gene was significantly higher or lower levels administration compared baseline. However, therapy, 861 transcripts found be differentially expressed, including interleukin chemokine receptors. Some are associated S1P pathway, such S1P5 kinase MAPK1, which increased expression. The fingolimod-induced reflect shift proportions T cell subsets, CCR7- effector memory being relatively frequency fingolimod-treated patients. In consequence, CCR7 mRNA reduced >80 % involved activation lymphocyte cytotoxicity Gene regulatory programs caused downstream signaling had only minor effects.