Dendritic Cells Transduced with SOCS1 Gene Exhibit Regulatory DC Properties and Prolong Allograft Survival

Abstract

SOCS1 is a key regulator of cytokine signaling and is important for maintaining balance in the immune system. It is thought to participate in negative feedback loops in cytokine signaling and may be an important signal for the regulation of dendritic cell (DC) maturation. However, it remains unclear whether DCs transduced with SOCS1 exhibit characteristics of regulatory DCs and induce allogeneic T-cell hyporesponsiveness. In this study, we constructed adenoviral vector coding SOCS1 (Ad-SOCS1) that can efficiently increase SOCS1 gene expression in bone marrow-derived dendritic cells. DCs transduced with Ad-SOCS1 (DC-SOCS1) expressed low levels of costimulatory and MHC molecules, were resistant to maturation and activation stimulation, induced allogeneic T-cell hyporesponsiveness, and promoted the generation of regulatory-like T cells in vitro. DC-SOCS1 pretreatment significantly prolonged the survival of allografts and led to a substantial increase in the generation of regulatory T cells. Our data suggest that SOCS1 inhibits DC maturation and induces regulatory DC generation, therefore possessing therapeutic potential to prevent rejection in organ transplantation.