Efficacy of Mycophenolic Acid Combined With KRP-203, a Novel Immunomodulator, in a Rat Heart Transplantation Model

Migration of CD4 T Cells and Dendritic Cells toward Sphingosine 1-Phosphate (S1P) Is Mediated by Different Receptor Subtypes: S1P Regulates the Functions of Murine Mature Dendritic Cells via S1P Receptor Type 3

“…This demonstrates their immunosuppressive effects against several types of autoimmune disorders (18,20,39,47). DCs migrate to lymph nodes through afferent lymphatic vessels, whereas T cells do so via high endothelial venules (1,2).…”

Change From Cyclosporine to Combination Therapy of Mycophenolic Acid With the New Sphingosine-1-phosphate Receptor Agonist, KRP-203, Prevents Host Nephrotoxicity and Transplant Vasculopathy in Rats

“…Indeed, intimal hyperplasia was not observed in our other study testing the efficacy of combination therapy of MPA with KRP-203 on the heart allograft between the same strains. 19 Therefore, in this study we used a rat aortic transplantation model in a high-responder, MHC-mismatched combination of DA to Lewis.…”

“…15 Our recent study has suggested that treatment with MPA or KRP-203 alone is insufficient and the combination therapy is effective for preventing acute rejection in the rat heart allograft. 19 Thus, we consider the combination therapy of MMF with an S1P agonist, such as KRP-203 or FTY720, as a potentially good alternative regimen to CIs, especially in patients with nephrotoxicity or renal dysfunction.…”

“…Quite recently, we demonstrated that this combination treatment of MPA with KRP-203 effectively protected r a t cardiac allograft from acute rejection in a highresponder combination of Dark Agouti (DA) to Lewis. 19 Thus, to focus on the transplant vasculopathy we selected an aortic transplantation model in the same combination in this study. 20 This conversion experiment was designed to mimic the clinical situation in which CsA (or FK 506) has to be withdrawn or reduced because of adverse effects such as nephrotoxicity.…”

“Inside-Out” Signaling of Sphingosine-1-Phosphate: Therapeutic Targets

“…KRP-203 prolonged graft survival and attenuated chronic rejection in rat heart allograft models, suggesting that it not only regulates T-cell responses but also those of B cells, in contrast to FTY720, which does not affect B cells (Mizushima et al, 2004). KRP-203 also markedly improved allogeneic immune responses in the heart trans-INSIDE-OUT SIGNALING OF S1P plantation model when used in combination with lowdose cyclosporine or MMF Suzuki et al, 2006). A similar positive effect was also noted in a rat renal allograft model in which KRP-203 in combination with a subtherapeutic dose of cyclosporine significantly prolonged skin and renal allograft survival and markedly improved graft kidney function .…”