The Effects of Fingolimod on T Cells and the Central Nervous System in the Pathogenesis of Multiple Sclerosis

Abstract

CCR7: C-C Chemokine Receptor Type 7; CNS: Central Nervous System; S1P: Sphingosine 1-Phosphate; S1P1: Sphingosine 1-Phosphate Receptor Subtype 1; TN: Naïve T Cell Knowledge of the immunopathology of multiple sclerosis (MS) within the central nervous system (CNS) continues to evolve and has been enhanced greatly by an understanding of the mode of action and effects of disease modifying therapies (DMTs). It is widely accepted that T cells play a critical role in the pathogenesis of MS, and immune cell infiltrates found in active CNS lesions are dominated by T cells and antigen-presenting cells [1,2]. Auto reactive T cells that migrate across the blood–brain barrier (BBB) are activated locally by immune cells in the CNS (microglia and astrocytes), leading to CNS inflammation (Figure 1) [3,4]. Indeed, the approved high-efficacy DMTs natalizumab and fingolimod exert effects on T cells by targeting facets of T-cell migration [5].