The S1P1 receptor-selective agonist CYM-5442 reduces the severity of acute GVHD by inhibiting macrophage recruitment.

摘要: FTY720, an agonist for four of the five known sphingosine-1-phosphate (S1P) receptors, has been reported to inhibit acute graft-versus-host disease (aGVHD). Because FTY720 functions through multiple S1P mechanism action one or more these receptors may account its side effects. Thus, selective receptor modulators are needed evaluate roles different and their therapeutic efficacies. In this study, we investigated effect S1P1-selective agonist, CYM-5442, on progression aGVHD. We showed that CYM-5442 significantly inhibited but did not prevent affect infiltration donor T cells into target organs, while number macrophages in GVHD organs was reduced by treatment. vivo proliferation assays suppressed CYM-5442. Further studies using human endothelial demonstrated treatment downregulated CCL2 CCL7 expression cells, therefore reducing migration monocytes, from which tissue originate. Our data demonstrate efficacy aGVHD possible action. The results suggest further investigations regarding as a potential regimen