Research paperDendritic cells that highly express SOCS1 induce T-cell hypo-responsiveness and prolong islet allograft survival

- SOCS1 genetic modification efficiently confers low expression of MHC and costimulatory molecules on mDCs.
- DC-SOCS1 induce T-cell hypo-responsiveness in vitro.
- DC-SOCS1 pretreated recipients had prolonged islet allograft survival in vivo.

The capability of dendritic cells (DCs) to induce an immune response or immune tolerance is dependent on their status. Suppressor of cytokine signaling 1 (SOCS1) is a pivotal regulator that participates in negative feedback of the JAK-STAT pathway, which plays a key role in the differentiation, activation, and maturation of DCs. DCs that highly express SOCS1 may modulate DCs, and induce immune anergy or immune tolerance. In this study, we transduced DCs with the recombinant adenovirus Ad5F35 to highly express SOCS1. The mechanisms by which DC-SOCS1 induces T-cell hypo-responsiveness were analyzed in vivo and in vitro. The data demonstrate that recipients treated with DC-SOCS1 had long islet allograft survival times, with a reduction of Th1 and Tc1 in both spleen and draining lymph nodes in vivo. In vitro assay revealed that DCs transduced with SOCS1 had low expression of major histocompatibility and costimulatory molecules, and potentiated the ability of DC-SOCS1 to induce T-cell hypo-responsiveness. Therefore, genetic modification of DCs with SOCS1 affects DC activation and maturation, inhibits T-cell proliferation and induces hypo-responsiveness, and prolongs islet allograft survival.