Induction of Experimental Autoimmune Encephalomyelitis (EAE) in type 1 Sphingosine 1‐Phosphate Receptor (S1P1) Transgenic Mice

S1P is a mast cell‐ and platelet‐derived mediator of diverse T cell functions that signals T cell traffic in lymphoid organs and their migration in tissues through their S1P 1 s. We investigated the role of T cell S1P 1 in murine high‐dose myelin oligodendrocyte glycoprotein (MOG)‐induced EAE in a transgenic (TG) mouse overexpressing S1P 1 selectively in T cells. The clinical signs of EAE were more severe and led to a markedly higher incidence of death by 2 weeks post injection in the S1P 1 transgenic mice. Enhanced EAE developed in S1P 1 TG mice in association with increased T cell generation of interferon gamma (IFN γ) and IL‐4, higher levels of serum IgG antibodies to MOG, and greater T cell proliferation after MOG stimulation, as early as day 14. The data support a critical role for the S1P‐S1P 1 axis in mediation of murine EAE and suggest that S1P 1 is a target for therapy of multiple sclerosis (Supported by pilot grant PP1061 to EJG by the Multiple Sclerosis Society).