M. Germana Sanna

TL;DR: The crystal structure of the sphingosine 1-phosphate receptor 1 fused to T4-lysozyme in complex with an antagonist sphingolipid mimic provides a detailed view of the molecular recognition and requirement for hydrophobic volume that activates S1P1, resulting in the modulation of immune and stromal cell responses.

TL;DR: S 1P1-selective agonists will be of broad utility in understanding cell functions in vitro, and vascular physiology in vivo, and the success of the chemical approach for S1P1 suggests that selective tools for the resolution of function across this broad lipid receptor family are now possible.

TL;DR: The sphingosine 1-phosphate (S1P) receptor signaling system, based in part on receptor subtype-selectivity and on differential attenuation of deleterious signals, now appears to be on the cusp of meaningful therapy for multiple sclerosis.

TL;DR: Chemical modulation reveals differences in S1P-S1P1 'set points' among tissues and highlights both mechanistic advantages (lymphocyte sequestration) and risks (pulmonary edema) of therapeutic intervention.

TL;DR: Two-photon imaging of living T cells in explanted lymph nodes after treatment with S1P1 agonists or antagonists is provided and results provide visualization of transendothelial migration of T cells into lymphatic sinuses and suggest that S1E2 agonists act mainly on endothelial cell S1p1 receptors to inhibit lymphocyte migration.