Recent evidence has shown that bone marrow stromal cells (BMSCs) may exhibit immuno-suppression activities through soluble mediators and direct cell-to-cell contact, but how these processes are modulated has been poorly understood.In this study, we show that the Notch signaling pathway participates in the modulation of BMSCs to elicit their immuno-suppressive roles.In a murine lethal acute graft versus host disease (aGvHD) model, BMSCs deficient for RBP-J, the critical transcription factor mediating signaling from all four mammalian Notch receptors, failed to delay the development of the disease.RBP-J deficient BMSCs were not able to inhibit the proliferation and activation of allogenic T-cells.Moreover, RBP-J deficient BMSCs could not down-regulate the expression of MHC Ⅱ and co-stimulation molecules CD80 and CD86 on dendritic cells (DCs).