CYM-5442 is anovel, potent and highly-selective S1P1 (Spingosine 1-Phosphate Receptor 1) agonist which reduces the severity of acute GVHD by inhibiting macrophage recruitment. CYM-5442 significantly inhibited but did not prevent aGVHD. CYM-5442 treatment downregulated CCL2 and CCL7 expression in endothelial cells, therefore reducing the migration of monocytes, from which tissue macrophages originate. CYM-5442 may be a potential therapeutic regimen for aGVHD.