Thus, the aim of this study was to characterize the immunomodulatory effect of the functional S1PR1 antagonist, siponimod, in phase III clinical trials for autoimmune disorders and of the competitive sphingosine 1-phosphate receptor subtype 1 (S1PR1) antagonist, TASP0277308, in pre-clinical development in an in vivo model of TBI in mice.
Here, we report that S1P receptor 1 (S1PR1) is elevated in reactive astrocytes in an autoimmunity independent mouse model of MS and that selective S1PR1 modulation is sufficient to ameliorate the loss of oligodendrocytes and demyelination.
Sphingosine 1-phosphate receptor 1 (S1P₁), an abundantly-expressed G protein-coupled receptor which regulates key vascular and immune responses, is a therapeutic target in autoimmune diseases.
Sphingosine-1-phosphate receptor subtype 1 (S1P1) is essential for lymphocyte egress from secondary lymphoid organs and is a validated drug target for the treatment of autoimmune disorders.
Mutant mice harboring an S1pr1 gene encoding phosphorylation-deficient receptors (S1P1(S5A)) developed severe experimental autoimmune encephalomyelitis (EAE) due to autoimmunity mediated by interleukin 17 (IL-17)-producing helper T cells (TH17 cells) in the peripheral immune and nervous system.
Disordered cellular and humoral immunity of S1P1-Tg mice thus may be attributable to both altered T cell traffic and depressed T cell functions, suggesting that S1P1-specific agonists may represent a novel therapeutic approach to autoimmunity and transplant rejection.