Regulation of the roles of sphingosine 1-phosphate and its type 1 G protein-coupled receptor in T cell immunity and autoimmunity

The lipid mediator sphingosine 1-phosphate (S1P) arid its type 1 G protein-coupled receptor (S1P(1)) affect mammalian immunity through alterations in thymocyte emigration. differentiation of T cell Subsets, lymphocyte trafficking in lymphoid organs arid other tissues, Tcell-dendritic cell arid T cell-B cell interactions, arid cytokine generation. Recent attention to effects of the S1P-S1P, axis on non-migration functions of lymphocytes includes delineation of a role in terminal differentiation arid survival of Th 17 effector cells and adaptive Treg cells of the CD4 T cell constellation, and a greater understanding of interactions of the S1P-S1P(1) axis with immune cytokines in lymphocyte survival and activities. This breadth of involvement of the S1P-S1P(1) axis in immune responses that often are altered in immunological diseases has provided many opportunities for novel therapeutic interventions. A spectrum of pharmacological and immunochemical agents is available that alter immunity by affecting either tissue arid fluid concentrations of S1P or levels of expression and signaling activities of S1P(1) .Such agents have so far been beneficial in the settings of autoimmunity arid rejection of transplanted organs, arid are likely to become valuable constituents of combined drug programs.