Figure 3.

Immunomodulatory activity of FTY720P. FTY720P as functional antagonist indirectly diminishes STAT-3 signaling by binding to S1PR1 on the cell surface, resulting in the internalization of S1PR1, and preventing S1P from binding to and activating this receptor. Binding of FTY720P to the receptor thus causes the receptor to be sequestered inside the cell, out of reach of S1P. Solid arrows indicate S1P-dependent signaling pathways; dashed arrows indicate the impact of functional antagonist—FTYY720P on signaling pathways. Abbreviations: S1P—sphingosine-1-phosphate; S1PR1—sphingosine-1-phosphate receptor1; FTY720P—fingolimod phosphate (S)-enantiomer; SK—sphingosine kinase; STAT3—signal transducer and activator of transcription 3; NFκB—nuclear factor kappa-light-chain-enhancer of activated B cells; CAC—colitis and cancer; red cross means that this pathway is inhibited.