Suppressor of cytokine signaling 3 (SOCS3) gene transfer prolongs the survival of the murine cardiac allograft by attenuating interleukin-17-producing alloreactive T-cell responses
Suppressor of cytokine signaling 3 (SOCS3) gene transfer prolongs the survival of the murine cardiac allograft by attenuating interleukin-17-producing alloreactive T-cell responses
复制标题
细胞因子信号传导抑制剂 3 (SOCS3) 基因转移通过减弱产生白细胞介素 17 的同种反应性 T 细胞反应来延长小鼠同种异体心脏移植物的存活时间
DOI：
10.1002/jgm.2760
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发表时间：
2014-03-01
影响因子：
3.5
通讯作者：
Fang, Min
中科院分区：
文献类型：
--
作者：
Xu, Qin;Zheng, Fang;Fang, Min
细胞因子信号抑制因子3（SOCS 3）是细胞因子信号的主要负反馈调节因子。我们研究了SOCS 3在小鼠同种异体心脏移植模型中的过表达可能通过减弱同种异体反应性T细胞应答而导致同种异体移植物的存活优势的假设。方法利用BALB/c（H-2（d））供体小鼠和C57 Bl/6 j（H-2（B））受体小鼠建立小鼠心脏移植模型。在移植前和移植后分别尾静脉注射真核表达质粒pEF-FLAG-I/mSOCS 3。结果SOCS 3在移植物和脾脏中的过表达可通过减少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CD 4（+）IL-17（+）细胞和CD 8（+）IL-17（+）细胞的数量，结论SOCS 3过表达可显著延缓心脏移植物急性排斥反应，其机制可能与移植物炎症前白细胞浸润减少和同种异体反应性IL-17（+）T细胞免疫功能受损有关。版权所有（c）2014约翰威利父子有限公司
BackgroundSuppressor 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.MethodsWith 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.ResultsOverexpression 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.ConclusionsOverexpression 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. Copyright (c) 2014 John Wiley & Sons, Ltd.