Donor bone-marrow suppressor of cytokine signaling-1-silenced dendritic cells prolong rat intestinal allograft survival.

Suppressor of cytokine signaling (SOCS) molecules belong to intracellular proteins that inhibit Janus kinase as well as signal transduction and activators of transcription pathways. In this study, we investigated whether SOCS-1-silenced dendritic cells (DCs) prolonged allograft survival in rat intestinal transplantation. Donor bone marrow-derived DCs were genetically transfected with SOCS-1 siRNA using liposomes. The level of SOCS-1 expression was quantitated by Western blots. DC function was assessed by MTT in mixed leukocyte reactions. We injected donor-derived SOCS-1 silenced DCs 7 days before heterotopic intestinal transplantation between SD donors and Wistar recipients. We compared untransfected DCs and silenced DCs to suppress allogeneic mixed leukocyte reactions. Recipients pretreated with SOCS-1-silenced DCs showed moderate survival prolongation with a mean allograft survival of 18.3 +/- 5.3 days (P < .05), compared with 6.4 +/- 2.0 days in the control group and 7.2 +/- 2.1 days in a control siRNA transfection DC group. The difference between untreated DCs group and the control group was not significant. In summary, SOCS-1 silenced DCs induced allogeneic T-cell hyporesponsiveness in vitro, promoting allograft survival in rat intestinal transplantation.