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.
Hong FuShaohua SongFang LiuZhijia NiXiaoyun ShenLiang XiaoGuoshan DingQuanxing Wang
T细胞免疫球蛋白黏蛋白(T-cell immunoglobulin and mucin,TIM)基因被发现表达于小鼠染色体11B1.1。TIM分子广泛存在于多种免疫细胞特别是抗原呈递细胞表面,可参与天然免疫和获得性免疫;某些TIM分子存在着多种配体,对T细胞具有双重作用;TIM的异常表达与多种疾病发生有关,可能作为药物治疗的新靶点;TIM与调节性T细胞(Tregs)相关性研究为移植免疫耐受诱导提供了新思路。因此,本文就TIM家族成员的免疫调节功能作一综述。
