Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
J Gene Med. 2014 Mar-Apr;16(3-4):66-74. doi: 10.1002/jgm.2760.
Suppressor of cytokine signaling 3 (SOCS3) is the main negative feedback regulator of cytokine signals. We investigated the hypothesis that overexpression of SOCS3 in a murine cardiac allograft transplantation model may result in a survival advantage of the allograft by attenuating alloreactive T-cell responses.
With the use of BALB/c (H-2(d) ) donor mice and C57Bl/6j (H-2(b) ) recipient mice, the murine cardiac transplantation model was established. Recipient mice received a tail intravenous injection with eukaryotic expression plasmid pEF-FLAG-I/mSOCS3 before and after transplantation. The heart beat of the grafts and immune responses were monitored.
Overexpression of SOCS3 within grafts and spleens can prolong the survival time of cardiac allografts by attenuating infiltration of inflammatory cells such as T cells and macrophages in the grafts, decreasing the number of CD4(+) IL-17(+) cells and CD8(+) IL-17(+) cells in spleens, as well as reducing the expression of STAT3 in grafts and phosphorylation of STAT3 in both grafts and spleens.
Overexpression of SOCS3 significantly delays cardiac allograft acute rejection, which is associated with reduced allograft proinflammatory leukocyte infiltration and impaired alloreactive IL-17(+) T cell immunity.
细胞因子信号转导抑制因子 3（SOCS3）是细胞因子信号的主要负反馈调节剂。我们假设在小鼠心脏移植模型中过表达 SOCS3 可能通过减弱同种反应性 T 细胞反应使移植物存活优势。
使用 BALB/c（H-2(d)）供体小鼠和 C57Bl/6j（H-2(b)）受体小鼠建立了小鼠心脏移植模型。受体小鼠在移植前后接受尾静脉注射真核表达质粒 pEF-FLAG-I/mSOCS3。监测移植物的心跳和免疫反应。
SOCS3 在移植物和脾脏中的过表达可以通过减轻移植物中炎性细胞（如 T 细胞和巨噬细胞）的浸润，减少脾脏中 CD4(+)IL-17(+)细胞和 CD8(+)IL-17(+)细胞的数量，以及降低移植物中 STAT3 的表达和 STAT3 在移植物和脾脏中的磷酸化来延长心脏同种异体移植物的存活时间。
SOCS3 的过表达显著延迟了心脏同种异体移植物的急性排斥反应，这与移植物促炎白细胞浸润减少和同种反应性 IL-17(+)T 细胞免疫受损有关。
